Leleti Rajender Reddy,* Mahavir Prashad

Supplementary Material (ESI) for Chemical Communications This journal is (c) The Royal Society of Chemistry 2009

Supporting Information

Asymmetric Synthesis of 2-Substituted Pyrrolidines by Addition of Grignard

Reagents to γ-Chlorinated N-(tert-Butanesulfinyl) Imine

Leleti Rajender Reddy,* Mahavir Prashad

Chemical Research and Development

Novartis Pharmaceuticals Corporation

One Health Plaza, East Hanover, New Jersey 07936, U.S.A.

Experimental Section

General Information: All the reactions were performed under dry nitrogen gas in

glasswares that was flame-dried and equipped with a magnetic stirring bar.

Tetrahydrofuran (THF) was freshly distilled from the sodium complex of benzophenone

before use. Thin-layer chromatography (TLC) was performed using E. Merck silica gel

60 F254 pre-coated plates (0.25 mm). Flash chromatography was performed using Baker

silica gel (40 μm particle size). All compounds were judged pure by TLC analysis (single

spot/ two solvent systems) using a UV lamp or PMA for detection purposes. 1H and 13C

NMR spectra were recorded on a Bruker FT-NMR spectrometer at 500 and 125 MHz,

respectively. High-resolution mass spectroscopy (HRMS) was carried out on a

ThermoFinnigan MAT-900 in electrospray mode. Other mass spectra were obtained on a

Micromass LCT in electrospray mode. Melting points were measured on a Büchi 533

melting point apparatus. All the reagents were purchased from commercial suppliers and

used without further purification.

General procedure (GP1) for the synthesis of γ-Chloro N-sulfinyl aldimine 1: A 500

mL, three-necked, round-bottomed flask was charged with 4-chlorobutanal (5) (100.0

mmol), THF (100 mL), tert-butanesulfinamide (100.0 mmol), and Ti(OEt)4 (110.0 mmol)

under nitrogen atm. The reaction mixture was stirred at rt for 16 h. After completion of

the reaction, charged the saturated NaCl solution (100 mL), ethyl acetate (100 mL) and

S1


stirred for 1 h at rt. The solids were removed by filtration and filtrate was washed with

water (2 × 50 mL). The organic phase was evaporated under vacuum to dryness to

obtained crude product. The crude product was purified by flash column chromatography

(silica gel, 10% ethyl acetate in heptanes) affords the pure γ-Chloro N-sulfinyl aldimine

1.

NS

OCl

(SS)-1

OCl

5H2N

SO

Ti(OEt)4, THF

HH

+

γ-chloro N-sulfinyl aldimine (SS) 1 : Following the general procedure (GP1), the

reaction of 4-chlorobutanal (5) (10.6 g, 100.0 mmol) with (SS)-tert-butanesulfinamide

(12.1 g, 100.0 mmol) and Ti(OEt)4 (25.0 g, 110.0 mmol) gave 20.4 g (98%) of pure γ-

Chloro N-sulfinyl aldimine (SS) 1 as viscous oil. [α]25D = + 231.1° (c 1.13, CHCl3).1H

NMR (501 MHz, CHLOROFORM-d) δ ppm 1.20 (s, 9 H) 2.07 - 2.20 (m, 2 H) 2.65 -

2.78 (m, 2 H) 3.56 - 3.68 (m, 2 H) 8.11 (t, J=3.94 Hz, 1 H). 13C NMR (125 MHz,

CHLOROFORM-d) δ 22.33, 27.99, 33.13, 43.97, 56.64, 167.87. HRMS (EI) Calcd for

C8H17ClNOS [M+H]: 210.0719, Found 210.0700.

NS

OCl

(RS)-1

OCl

5H2N

SO

Ti(OEt)4, THF

HH

+

γ-chloro N-sulfinyl aldimine (RS) 1 : Following the general procedure (GP1), the

reaction of 4-chlorobutanal (5) (1.06 g, 10.0 mmol) with (RS)-tert-butanesulfinamide (1.2

g, 10.0 mmol) and Ti(OEt)4 (2.5 g, 11.0 mmol) gave 1.98 g (95%) of pure γ-Chloro N-

sulfinyl aldimine (RS) 1 as viscous oil. [α]25D = + 229.2° (c 1.01, CHCl3). 1H NMR (500

MHz, CHLOROFORM-d) δ ppm 1.20 (s, 9 H) 2.14 (dd, J=6.46, 4.26 Hz, 2 H) 2.66 -

2.75 (m, 2 H) 3.58 - 3.69 (m, 2 H) 8.11 (t, J=3.94 Hz, 1 H). 13C NMR (125 MHz,

CHLOROFORM-d) δ 22.34, 28.00, 33.13, 43.97, 56.65, 167.

S2


General Procedure (GP2) for the Synthesis 2-substituted pyrrolidines: To a solution

of aldimine 1 (5 mmol) in CH2Cl2 (25 mL) at –78 °C under nitrogen was added the

Grignard reagents 6 (6 mmol). After stirring for 5 h at –78 °C reaction mixture was

quenched with saturated NH4Cl (20 mL) then separated the organic layer and washed

with water. The organic layer was removed in vacuum to give crude product. The crude

product was dissolved in THF (20 mL) at 23 °C under nitrogen was added the LiHMDS

(7.5 mmol). After stirring for 1 h at 23 °C reaction mixture was quenched with saturated

NH4Cl (20 mL) then extracted with ethyl acetate (2 x 25 mL). The combined organic

layers were washed with water (20 mL) and solvent was removed in vacuum to give

crude product. The crude product were purified by column chromatography (silica gel,

ethyl acetate/hexanes) affords the pure 2-substituted pyrrolidines 4.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6a 4a

H

MgCl

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-phenyl-pyrrolidine (4a) : Following the

general procedure (GP2), the reaction of γ-chloro N-sulfinyl aldimine (SS)-1 (1.05 g, 5.0

mmol) with phenylmagnisum chloride (3.0 mL, 6.0 mmol) and LiHMDS (7.5 mL, 7.5

mmol) afforded pyrrolidine 4a (1.14 g, 91%) as a white solid, mp = 80-81 °C, [α]25D = −

140.4° (c 1.07, CHCl3). 1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.05 (s, 9 H)

1.66 - 1.95 (m, 3 H) 2.16 (dd, J=11.35, 8.51 Hz, 1 H) 3.45 - 3.61 (m, 1 H) 3.61 - 3.73 (m,

1 H) 5.07 (dd, J=8.20, 2.84 Hz, 1 H) 7.16 - 7.39 (m, 5 H). 13C NMR (125 MHz,

CHLOROFORM-d) δ 23.11, 24.22, 36.64, 54.92, 57.47, 126.53, 126.36, 144.67. HRMS

(EI) Calcd for C14H22NOS [M+H]: 252.1402, Found 252.1413.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(RS)-1 6a ent-4a

H

MgCl

(R)-1-((R)-2-Methyl-propane-2-sulfinyl)-2-phenyl-pyrrolidine (ent-4a) : Following

the general procedure (GP2), the reaction of γ-chloro N-sulfinyl aldimine (RS)-1 (1.05 g,

5.0 mmol) with phenylmagnisum chloride (3.0 mL, 6.0 mmol) and LiHMDS (7.5 mL, 7.5

mmol) afforded pyrrolidine ent-4a (1.12 g, 90%) as a white solid, mp = 80-82 °C, [α]25D

S3


= + 141.2° (c 1.10, CHCl3). 1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.05 (s)

1.82 (m) 2.16 (dd, J=11.35, 8.51 Hz) 3.56 (m) 3.66 (m) 5.07 (dd, J=8.04, 2.68 Hz) 7.26

(m). ). 13C NMR (125 MHz, CHLOROFORM-d) δ 23.09, 24.21, 36.64, 54.90, 57.46,

126.52, 126.36, 144.66. HRMS (EI) Calcd for C14H22NOS [M+H]: 252.1402, Found

252.1422.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6b 4b

H

MgBrBr

Br

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-(4-bromophenyl)-pyrrolidine (4b):

Following the general procedure (GP2), the reaction of γ-chloro N-sulfinyl aldimine (SS)-

1 (1.05 g, 5.0 mmol) with 4-bromophenylmagnisum bromide (6.0 mL, 6.0 mmol) and

LiHMDS (7.5 mL, 7.5 mmol) afforded pyrrolidine 4b (1.35 g, 83%) as white solid, mp

= 100-112 °C, [α]25D = − 164.3° (c 1.13, CHCl3). 1H NMR (501 MHz, CHLOROFORM-

d) δ ppm 1.05 (s, 9 H) 1.60 - 1.93 (m, 3 H) 2.16 (dd, J=11.98, 9.14 Hz, 1 H) 3.47 - 3.58

(m, 1 H) 3.61 - 3.70 (m, 1 H) 5.02 (dd, J=8.20, 2.84 Hz, 1 H) 7.14 (d, J=8.51 Hz, 2 H)

7.37 - 7.49 (m, 2 H). 13C NMR (125 MHz, CHLOROFORM-d) δ 23.06, 24.19, 36.49,

54.86, 56.96, 57.48, 120.36, 128.28, 131.48, 143.78. HRMS (EI) Calcd for C14H21BrNOS

[M+H]: 330.0527, Found 330.0539.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(RS)-1 6b ent-4b

H

MgBrBr

Br

(R)-1-((R)-2-Methyl-propane-2-sulfinyl)-2-(4-bromophenyl)-pyrrolidine (ent-4b):

Following the general procedure (GP2), the reaction of γ-chloro N-sulfinyl aldimine (RS)-

1 (1.05 g, 5.0 mmol) with 4-bromophenylmagnisum bromide (6.0 mL, 6.0 mmol) and

LiHMDS (7.5 mL, 7.5 mmol) afforded pyrrolidine ent-4b (1.39 g, 85%) as white solid,

mp = 110-111 °C, [α]25D = + 163.1° (c 1.02, CHCl3). 1H NMR (501 MHz,

CHLOROFORM-d) δ ppm 1.05 (s, 9 H) 1.66 - 1.94 (m, 3 H) 2.08 - 2.21 (m, 1 H) 3.51 -

3.58 (m, 1 H) 3.60 - 3.68 (m, 1 H) 5.02 (dd, J=8.20, 2.84 Hz, 1 H) 7.13 (d, J=8.20 Hz, 2

H) 7.43 (d, J=8.20 Hz, 2 H). 13C NMR (125 MHz, CHLOROFORM-d) δ 23.07, 24.19,

S4


36.50, 54.89, 56.96, 57.50, 120.36, 128.29, 131.49, 143.81. HRMS (EI) Calcd for

C14H21BrNOS [M+H]: 330.0527, Found 330.0529.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6c 4c

H

MgCl

Me

Me

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-(4-methylphenyl)-pyrrolidine (4c):


1 (1.05 g, 5.0 mmol) with 4-methylphenylmagnisum chloride (2.0 mL, 6.0 mmol) and

LiHMDS (7.5 mL, 7.5 mmol) afforded pyrrolidine 4c (1.13 g, 86%) as white solid, mp

= 98-100 °C, [α]25D = − 150.2° (c 1.16, CHCl3). 1H NMR (501 MHz, CHLOROFORM-

d) δ ppm 1.06 (s, 9 H) 1.66 - 1.77 (m, 1 H) 1.78 - 1.92 (m, 2 H) 2.08 - 2.23 (m, 1 H) 2.32

(s, 3 H) 3.48 - 3.59 (m, 1 H) 3.61 - 3.71 (m, 1 H) 5.02 (dd, J=8.04, 2.68 Hz, 1 H) 7.07 -

7.18 (m, 4 H). 13C NMR (125 MHz, CHLOROFORM-d) δ 21.01, 23.14, 36.66, 54.57,

57.45, 126.46, 129.03, 136.09, 141.58. HRMS (EI) Calcd for C15H24NOS [M+H]:

266.1579, Found 265.1589.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6d 4d

H

MgCl

MeO

OMe

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-(4-methoxyphenyl)-pyrrolidine (4d):


1 (1.05 g, 5.0 mmol) with 4-methoxyphenylmagnisum bromide (12.0 mL, 6.0 mmol) and

LiHMDS (7.5 mL, 7.5 mmol) afforded pyrrolidine 4d (1.20 g, 88%) as white solid, mp

= 85-87 °C, [α]25D = − 140.98° (c 1.07, MeOH). 1H NMR (501 MHz, CHLOROFORM-

d) δ ppm 1.07 (s, 9 H) 1.74 (dd, J=7.72, 3.94 Hz, 1 H) 1.78 - 1.93 (m, 2 H) 2.05 - 2.20

(m, 1 H) 3.43 - 3.58 (m, 1 H) 3.61 - 3.70 (m, 1 H) 3.79 (s, 3 H) 4.99 (dd, J=7.88, 2.84 Hz,

1 H) 6.85 (d, 2 H) 7.16 (d, J=8.83 Hz, 21 H). 13C NMR (125 MHz, CHLOROFORM-d) δ

23.15, 24.16, 36.62, 54.21, 55.18, 57.42, 113.72, 127.63, 136.63, 158.29. HRMS (EI)

Calcd for C15H24NO2S [M+H]: 282.1528, Found 282.1526.

S5


NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(RS)-1 6d ent-4d

H

MgCl

MeO

OMe

(R)-1-((R)-2-Methyl-propane-2-sulfinyl)-2-(4-methoxyphenyl)-pyrrolidine (ent-4d):


1 (1.05 g, 5.0 mmol) with 4-methoxyphenylmagnisum bromide (12.0 mL, 6.0 mmol) and

LiHMDS (7.5 mL, 7.5 mmol) afforded pyrrolidine 4d (1.17 g, 83%) as white solid, mp

= 85-86 °C, [α]25D = + 139.98° (c 1.13, MeOH). 1H NMR (501 MHz, CHLOROFORM-

d) δ ppm 1.06 (s) 1.69 - 1.91 (m) 2.13 (dd, J=11.82, 9.30 Hz) 3.47 - 3.56 (m) 3.79 (s)

5.00 (dd, J=7.88, 3.15 Hz) 6.85 (d, J=8.51 Hz) 7.16 (d, J=8.51 Hz). 13C NMR (125 MHz,

CHLOROFORM-d) δ 23.17, 24.16, 36.65, 55.23, 57.46, 113.73, 127.66, 136.69, 158.29.

HRMS (EI) Calcd for C15H24NO2S [M+H]: 282.1528, Found 282.1519.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6e 4e

H

MgBr

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-(4-t-butylphenyl)-pyrrolidine (4e):


1 (1.05 g, 5.0 mmol) with 4-t-butylphenylmagnisum bromide (6.0 mL, 6.0 mmol) and

LiHMDS (7.5 mL, 7.5 mmol) afforded pyrrolidine 4e (1.30 g, 85%) as white solid, mp

= 55-56 °C, [α]25D = − 140.03° (c 0.98, MeOH). 1H NMR (501 MHz, CHLOROFORM-

d) δ ppm 1.06 (s, 9 H) 1.31 (s, 9 H) 1.71 - 1.92 (m, 3 H) 2.07 - 2.20 (m, 1 H) 3.45 - 3.54

(m, 1 H) 3.60 - 3.72 (m, 1 H) 5.02 (dd, J=8.04, 2.36 Hz, 1 H) 7.16 (d, J=8.20 Hz, 2 H)

7.31 (d, J=8.20 Hz, 2 H). 13C NMR (125 MHz, CHLOROFORM-d) δ 23.18, 24.14,

31.39, 34.40, 36.49, 54.10, 57.48, 57.89, 125.17, 126.17, 141.28, 149.35. HRMS (EI)

Calcd for C18H30BrNOS [M+H]: 308.2048, Found 330.0530.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6f 4f

H

MgCl

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-cyclohexyl pyrrolidine (4f):

S6



1 (1.05 g, 5.0 mmol) with cyclohexylmagnisum chloride (3.0 mL, 6.0 mmol) and

LiHMDS (7.5 mL, 7.5 mmol) afforded pyrrolidine 4f (1.01 g, 90%) as viscous oil,

[α]25D = − 40.0° (c 1.29, CHCl3). 1H NMR (501 MHz, CHLOROFORM-d) δ ppm 0.86 -

1.06 (m, 2 H) 1.06 - 1.18 (m, 1 H) 1.14 - 1.31 (m, 11 H) 1.59 - 1.83 (m, 1 H) 3.11 - 3.25

(m, 1 H) 3.27 - 3.42 (m, 1 H) 3.50 - 3.64 (m, 1 H). 13C NMR (125 MHz,

CHLOROFORM-d) δ 23.49, 25.13, 26.30, 26.55, 27.13, 27.48, 30.73, 41.57, 50.06,

57.59, 62.73, HRMS (EI) Calcd for C14H28NOS [M+H]: 258.1892, Found 258.1858.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6g 4g

H

MgCl

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-t-butyl pyrrolidine (4g):


1 (1.05 g, 5.0 mmol) with t-butylmagnisum chloride (3.0 mL, 6.0 mmol) and LiHMDS

(7.5 mL, 7.5 mmol) afforded pyrrolidine 4g (0.97 g, 84%) as viscous oil, [α]25D = −

76.6° (c 1.04, CHCl3). 1H NMR (501 MHz, CHLOROFORM-d) � ppm 0.96 (s, 9 H)

1.25 (s, 9 H) 1.70 - 1.93 (m, 4 H) 3.08 - 3.19 (m, 1 H) 3.28 - 3.38 (m, 1 H) 3.50 (dd,

J=8.04, 4.26 Hz, 1 H). 13C NMR (125 MHz, CHLOROFORM-d) δ 23.75, 25.12, 27.02,

27.40, 35.85, 48.28, 58.75, 68.30. HRMS (EI) Calcd for C12H25NOS [M+H]: 232.1732,

Found 232.1729.

NS

O+

1) CH2Cl2, -78 oC, 5 hCl

2) LiHMDS, THF, 1h

NS O

(SS)-1 6h 4h

H

MgCl

(S)-1-((S)-2-Methyl-propane-2-sulfinyl)-2-vinyl pyrrolidine (4h):


1 (1.05 g, 5.0 mmol) with vinylmagnisum chloride (3.0 mL, 6.0 mmol) and LiHMDS (7.5

mL, 7.5 mmol) afforded pyrrolidine 4 h (0.82 g, 82%) as viscous oil, [α]25D = − 72.6° (c

1.14, CHCl3). 1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.18 (s, 9 H) 1.50 - 1.65

(m, 1 H) 1.67 - 1.79 (m, 1 H) 1.82 - 1.95 (m, 1 H) 2.02 (dd, J=11.98, 4.10 Hz, 1 H) 2.70 -

2.87 (m, 1 H) 3.71 - 3.81 (m, 1 H) 4.03 (q, J=7.36 Hz, 1 H) 5.06 (d, J=10.72 Hz, 1 H)

S7


5.16 (d, J=17.02 Hz, 1 H) 5.59 - 5.76 (m, 1 H). 13C NMR (125 MHz, CHLOROFORM-d)

δ 23.78, 25.79, 32.60, 41.26, 57.01, 67.93, 115.73, 140.18. HRMS (EI) Calcd for

C10H19NOS [M+H]: 202.1266, Found 202.1253.

General Procedure (GP3) for the deprotection of tert-butanesulfinyl group from 4:

To a solution of 4 (2 mmol) in MeOH (10 mL) was added 4 M HCl solution (in dioxane,

2 mL). After the mixture was stirred at room temperature for 30 min, the mixture was

concentrated to dryness and carefully dissolved in water (20 mL). The aqueous layer was

washed with ethyl acetate (2 x 20 mL) and neutralized with 6N NaOH solution to pH

~13. Then, the resulting aqueous solution was extracted with ethyl acetate (3 × 30 mL).

The combined organic layers were washed with brine and then dried over anhydrous

Na2SO4. The organic layer was concentrated to dryness to obtained pure 2-substituted

pyrrolidins 7.

NS

O 1. 4 M HCl, dioxane, 1 h2. 6 N NaOH H

N

4a 7a (S)-2-Phenyl pyrrolidine (7a): Following the general procedure (GP3), the reaction of

4a (0.504 g, 2.0 mmol) with 4 M HCl solution (in dioxane, 2 mL) gives the (S)-2-phenyl

pyrrolidine (7a) (291 mg, 99%) as viscous oil, [α]25D = − 64.4° (c 1.02, CH2Cl2). 1H

NMR (501 MHz, CHLOROFORM-d) δ ppm 1.61 - 1.73 (m, 1 H) 1.79 - 2.02 (m, 3 H)

2.14 - 2.24 (m, 1 H) 2.98 - 3.06 (m, 1 H) 3.17 - 3.25 (m, 1 H) 4.12 (t, J=7.72 Hz, 1 H)

7.18 - 7.27 (m, 2 H) 7.28 - 7.40 (m, 3 H). 13C NMR (125 MHz, CHLOROFORM-d) δ

25.58, 34.29, 46.94, 62.57, 126.54, 126.98, 128.35, 144.66. HRMS (EI) Calcd for

C10H14N [M+H]: 148.1126, Found 148.1086.

NS

O 1. 4 M HCl, dioxane, 1 h2. 6 N NaOH H

N

ent-4a ent-7a (R)-2-Phenyl pyrrolidine (ent-7a): Following the general procedure (GP3), the reaction

of ent-4a (0.504 g, 2.0 mmol) with 4 M HCl solution (in dioxane, 2 mL) gives the (R)-2-

S8


S9

NS

O

(R)-2-(4-Bromophenyl)-pyrrolidine (ent-7b): Following the general procedure (GP3),

the reaction of ent-4b (658 mg, 2.0 mmol) with 4 M HCl solution (in dioxane, 2 mL)

gives the (R)-2-(4-bromophenyl)-pyrrolidine (ent-7b) (440 mg, 97%) as viscous oil,

[α]25D = + 52.1° (c 1.01, CH2Cl2). 1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.59

(dd, J=12.30, 9.14 Hz) 1.85 (m) 2.16 (m) 2.99 (m) 3.15 (m) 4.05 (t, J=7.57 Hz) 7.22 (d,

J=8.20 Hz) 7.41 (d, J=8.20 Hz). ). 13C NMR (125 MHz, CHLOROFORM-d) δ 25.50,

34.44, 46.93, 61.87, 120.36, 128.29, 131.33, 144.02. HRMS (EI) Calcd for C10H13BrN

[M+H]: 226.0231, Found 226.0217.

(S)-2-(4-Bromophenyl)-pyrrolidine (7b): Following the general procedure (GP3), the

reaction of 4b (658 mg, 2.0 mmol) with 4 M HCl solution (in dioxane, 2 mL) gives the

(S)-2-(4-bromophenyl) pyrrolidine (7b) (442 mg, 98%) as viscous oil, [α]25D = − 51.9°

(c 1.27, CH2Cl2). 1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.50 - 1.64 (m, 1 H)

1.74 - 1.97 (m, 3 H) 2.09 - 2.21 (m, 1 H) 2.93 - 3.05 (m, 1 H) 3.11 - 3.20 (m, 1 H) 4.05 (t,

J=7.72 Hz, 1 H) 7.22 (d, J=8.20 Hz, 2 H) 7.40 (d, J=8.51 Hz, 2 H). 13C NMR (125 MHz,

CHLOROFORM-d) δ 25.50, 34.47, 46.93, 61.82, 120.27, 128.25, 131.27, 144.17.

HRMS (EI) Calcd for C10H13BrN [M+H]: 226.0231, Found 226.0185.

phenyl pyrrolidine (ent-7a) (290 mg, 98%) as viscous oil, [α]25D = +64.2° (c 1.02,

CH2Cl2). 1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.68 (m) 1.88 (m) 2.17 (m)

2.74 (br. s.) 2.99 (m) 3.18 (m) 4.09 (t, J=7.88 Hz) 7.28 (m). 13C NMR (125 MHz,

CHLOROFORM-d) δ 25.53, 34.20, 46.86, 62.60, 126.58, 126.87, 128.38, 144.34. HRMS

(EI) Calcd for C10H14N [M+H]: 148.1126, Found 148.1112.

1. 4 M HCl, dioxane, 1 h2. 6 N NaOH

NS

O

HN

4b 7b

Br Br

1. 4 M HCl, dioxane, 1 h2. 6 N NaOH H

N

ent-4b ent-7b

Br Br


5/14/2009 2:35:32 PM

Acquisition Time (sec) 3.1719 Comment 3140-67-pure PROTON16 CDCl3 u leletra1 2 Date 14 Apr 2009 17:38:08Date Stamp 14 Apr 2009 17:38:08 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-67-pure_010001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner drinkdo1 Points Count 32768 Pulse Sequence zg30Receiver Gain 57.00 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3093.2183 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.20 (s, 9 H) 2.07 - 2.20 (m, 2 H) 2.65 - 2.78 (m, 2 H) 3.56 - 3.68 (m, 2 H) 8.11 (t, J=3.94 Hz, 1 H)VerticalScaleFactor = 1

3140-67-pure_010001r M05(s)

1.20

10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

9.02.02.02.00.9

M01(t)

M04(m)M03(m)

M02(m)

2.13

2.132.14

2.15

2.16

2.16

2.70

2.702.

712.

712.

72

3.61

3.62

3.633.63

3.64

3.658.10

8.11

8.12

N

Cl

SO

S1


5/14/2009 2:39:59 PM

Acquisition Time (sec) 1.0912 Comment 3140-67-pure C13CPD256 CDCl3 u leletra1 2 Date 14 Apr 2009 17:46:40Date Stamp 14 Apr 2009 17:46:40 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-67-pure_011001rFrequency (MHz) 125.88 Nucleus 13C Number of Transients 256 Origin spectOriginal Points Count 32768 Owner drinkdo1 Points Count 32768 Pulse Sequence zgpg30Receiver Gain 13004.00 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 12587.9785 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000

VerticalScaleFactor = 13140-67-pure_011001r

200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0Chemical Shift (ppm)

22.3

3

27.9

9

33.1

3

43.9

7

56.6

476.8

077

.05

77.3

1

167.

87

N

Cl

SO

S2


Acquisition Time (sec) 3.1719 Comment 3140-67-R PROTON16 CDCl3 u leletra1 22 Date 16 Jul 2009 21:24:16Date Stamp 16 Jul 2009 21:24:16 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-67-R_010001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zg30Receiver Gain 101.60 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3089.2134 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.20 (s, 9 H) 2.14 (dd, J=6.46, 4.26 Hz, 2 H) 2.66 - 2.75 (m, 2 H) 3.58 - 3.69 (m, 2 H) 8.11 (t, J=3.94 Hz, 1 H)

VerticalScaleFactor = 13140-67-R_010001r

9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

M05(s)

9.22.02.02.00.9

M01(t)M03(m)

M02(m)M04(dd)

1.20

2.132.14

2.15

2.16

2.702.71

2.71

2.72

3.61

3.623.

633.

633.

643.

64

8.108.

118.

12

NS

OCl H

S3


Acquisition Time (sec) 1.0912 Comment 3140-67-R C13CPD256 CDCl3 u leletra1 22 Date 16 Jul 2009 21:39:12Date Stamp 16 Jul 2009 21:39:12 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-67-R_011001rFrequency (MHz) 125.88 Nucleus 13C Number of Transients 256 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zgpg30Receiver Gain 6502.00 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 12587.9785 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000


192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0Chemical Shift (ppm)

22.3

4

28.0

0

33.1

3

43.9

7

56.6

5

76.7

877

.04

77.2

9

167.

88

NS

OCl H

S4


5/14/2009 2:48:14 PM

Acquisition Time (sec) 3.1719 Comment 3140-81-F PROTON1024 CDCl3 u leletra1 21 Date 10 May 2009 17:57:20Date Stamp 10 May 2009 17:57:20 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-81-F_012001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 1024 Origin spectOriginal Points Count 32768 Owner drinkdo1 Points Count 32768 Pulse Sequence zg30Receiver Gain 71.80 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3083.4517 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.05 (s, 9 H) 1.66 - 1.95 (m, 3 H) 2.16 (dd, J=11.35, 8.51 Hz, 1 H) 3.45 - 3.61 (m, 1 H) 3.61 - 3.73 (m, 1 H) 5.07 (dd, J=8.20, 2.84 Hz, 1 H) 7.16 - 7.39 (m, 5 H)

VerticalScaleFactor = 13140-81-F_012001r

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

M07(s)

1.05

9.03.21.01.01.05.0

M03(m)M02(dd) M05(dd)

M04(m)M01(m)

M06(m)

0.00

1.741.83

1.85

1.851.86

1.881.89

2.14

2.16

2.17

2.183.55

3.563.

573.

643.

653.

663.

663.67

3.685.06

5.06

5.08

5.08

7.197.

217.

227.247.

257.

297.31

7.32

N

SO

S5


5/14/2009 2:54:02 PM

Acquisition Time (sec) 1.0912 Comment 3140-81-F C13CPD2048 CDCl3 u leletra1 21 Date 10 May 2009 18:57:04Date Stamp 10 May 2009 18:57:04 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-81-F_013001rFrequency (MHz) 125.88 Nucleus 13C Number of Transients 2048 Origin spectOriginal Points Count 32768 Owner drinkdo1 Points Count 32768 Pulse Sequence zgpg30Receiver Gain 4096.00 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 14477.7813 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000


210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0Chemical Shift (ppm)

23.1

124

.22

36.6

4

54.9

257

.47

76.8

077

.05

77.3

1

126.

5312

8.36

144.

67

N

SO

S6



1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.05 (s) 1.82 (m) 2.16 (dd, J=11.35, 8.51 Hz) 3.56 (m) 3.66 (m) 5.07 (dd, J=8.04, 2.68 Hz) 7.26 (m)



M07(s)

1.05

9.13.21.11.01.05.2

M03(m)

M04(m)

M02(dd) M05(dd)

M01(m)M06(m)

0.00

1.77

1.83

1.851.86

1.87

1.88

1.89

2.14

2.16

2.17

2.183.55

3.553.

573.

583.

643.

653.

663.

673.

685.06

5.06

5.07

5.08

7.197.

217.

227.24

7.25

7.297.31

7.32

N

SO

S7





23.0

924

.21

36.6

3

54.9

057

.46

57.5

1

76.8

077

.05

77.3

0

126.

5212

8.36

144.

66N

SO

S8


5/14/2009 3:11:08 PM

Acquisition Time (sec) 3.1719 Comment PROTON CDCl3 u leletra1 11 Date 23 Oct 2008 06:36:48Date Stamp 23 Oct 2008 06:36:48 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3105-106-F_010001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zg30Receiver Gain 50.80 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3097.0930 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.05 (s, 9 H) 1.60 - 1.93 (m, 3 H) 2.16 (dd, J=11.98, 9.14 Hz, 1 H) 3.47 - 3.58 (m, 1 H) 3.61 - 3.70(m, 1 H) 5.02 (dd, J=8.20, 2.84 Hz, 1 H) 7.14 (d, J=8.51 Hz, 2 H) 7.37 - 7.49 (m, 2 H)



M08(s)

9.13.11.01.01.02.02.0

M04(m)

M05(m)M02(d)

M01(m)

M03(dd) M06(dd)

M07(m)

7.44 7.

427.

427.

307.

147.

13

5.03

5.03

5.02

5.01

3.64

3.63 3.63

3.61

3.57 3.

56

3.54 3.54

2.16

2.15

2.13

1.89

1.88

1.87 1.87

1.80

1.79

1.72

1.70

1.27

1.05

N

SO Br

S9


5/14/2009 3:18:24 PM

Acquisition Time (sec) 1.0912 Comment C13CPD256 CDCl3 u leletra1 11 Date 22 Oct 2008 19:58:56Date Stamp 22 Oct 2008 19:58:56 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3105-106-F_012001rFrequency (MHz) 125.88 Nucleus 13C Number of Transients 256 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zgpg30Receiver Gain 11585.20 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 12587.9785 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000



23.0

624

.19

36.4

9

54.8

656.9

657

.48

76.8

477

.10

77.3

5

120.

36

128.

28131.

48

143.

78N

SO Br

S10



1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.05 (s, 9 H) 1.66 - 1.94 (m, 3 H) 2.08 - 2.21 (m, 1 H) 3.51 - 3.58 (m, 1 H) 3.60 - 3.68 (m, 1 H) 5.02 (dd, J=8.20, 2.84 Hz, 1 H) 7.13 (d, J=8.20 Hz, 2 H) 7.43 (d, J=8.20 Hz, 2 H)


9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)

M08(s)

1.05

8.83.21.01.01.01.91.9

M01(d)

M05(m)

M02(d)

M03(dd)M04(m)

M06(m)

M07(m)

5.01

5.02

5.03

5.03

7.137.147.43

7.44

N

S O Br

S11





23.0

724

.1936

.50

54.8

956

.96

57.5

0

76.8

077

.05

77.3

1

120.

36

128.

2913

1.49

143.

81N

S O Br

S12


Acquisition Time (sec) 3.1719 Comment Date 09 Jun 2009 18:35:44Date Stamp 09 Jun 2009 18:35:44 File NameFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zg30Receiver Gain 35.90 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3093.0684 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.07 (s, 9 H) 1.74 (dd, J=7.72, 3.94 Hz, 1 H) 1.78 - 1.93 (m, 2 H) 2.05 - 2.20 (m, 1 H) 3.43 - 3.58 (m, 1 H) 3.61 - 3.70 (m, 1 H) 3.79 (s, 3 H) 4.99 (dd, J=7.88, 2.84 Hz, 1 H) 6.85 (d, 2 H) 7.16 (d, J=8.83 Hz, 21 H)3170-5-F_010001r


M10(s)

9.11.01.21.11.01.02.02.0

M01(d)

M04(s)

M03(dd)

M02(d)

M09(dd)M05(m) M07(m)

M06(m) M08(m)

1.06

1.08

1.721.83

1.83

1.84

1.851.85

1.862.

102.

122.

132.

153.50

3.513.

523.

653.

653.

663.

79

4.98

4.99

5.00

5.00

6.846.

866.

86

7.15

7.17

N

SO OMe

S13


Acquisition Time (sec) 1.0912 Comment Date 09 Jun 2009 18:48:32Date Stamp 09 Jun 2009 18:48:32 File NameFrequency (MHz) 125.88 Nucleus 13C Number of Transients 256 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zgpg30Receiver Gain 13004.00 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 12587.9785 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000

3170-5-F_011001r


23.1

524

.16

36.6

2

54.2

155

.18

57.4

2

76.8

477

.09

77.3

4

113.

72

127.

63

136.

63

158.

29

N

SO OMe

S14


Acquisition Time (sec) 3.1719 Comment 3140-OMe-R PROTON16 CDCl3 u leletra1 40 Date 24 Jul 2009 16:17:04Date Stamp 24 Jul 2009 16:17:04 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-OMe-R_010001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zg30Receiver Gain 256.00 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3080.1375 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.06 (s) 1.69 - 1.91 (m) 2.13 (dd, J=11.82, 9.30 Hz) 3.47 - 3.56 (m) 3.79 (s) 5.00 (dd, J=7.88, 3.15 Hz) 6.85 (d, J=8.51 Hz) 7.16 (d, J=8.51 Hz)

VerticalScaleFactor = 13140-OMe-R_010001r

10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

M08(s)

9.13.11.01.03.01.02.02.0

M04(s)

M01(d)

M03(dd)

M02(d)

M05(m) M06(dd)

M07(m)

0.00

1.06

1.67

1.821.841.85

1.86

1.86

1.87

1.87

2.10

2.12

2.133.51

3.513.53

3.65

3.65

3.66

3.79

4.99

4.99

5.00

5.01

6.846.

86

7.15

7.17

7.26

N

S O OMe

S15


Acquisition Time (sec) 1.0912 Comment 3140-OMe-R C13CPD256 CDCl3 u leletra1 40 Date 24 Jul 2009 16:29:52Date Stamp 24 Jul 2009 16:29:52 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-OMe-R_011001rFrequency (MHz) 125.88 Nucleus 13C Number of Transients 256 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zgpg30Receiver Gain 8192.00 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 12587.9785 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000

VerticalScaleFactor = 13140-OMe-R_011001r


23.1

724

.1636

.65

55.2

357

.46

76.7

677.0

277

.27

113.

73

127.

66

136.

69

158.

29

N

S O OMe

S16


Acquisition Time (sec) 3.1719 Comment 3170-8-12f PROTON16 CDCl3 u dasso8 3 Date 15 Jun 2009 14:49:36Date Stamp 15 Jun 2009 14:49:36 File Name C:\Documents and Settings\leletra1\Desktop\sonia\3170-8-12f_010001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zg30Receiver Gain 57.00 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3082.5256 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.06 (s, 9 H) 1.66 - 1.77 (m, 1 H) 1.78 - 1.92 (m, 2 H) 2.08 - 2.23 (m, 1 H) 2.32 (s, 3 H) 3.48 - 3.59 (m, 1 H) 3.61 - 3.71 (m, 1 H) 5.02 (dd, J=8.04, 2.68 Hz, 1 H) 7.07 - 7.18 (m, 4 H)3170-8-12f_010001r


9.21.11.13.11.01.04.0

M09(s)

M05(s)

M08(m)M03(m)

M04(m)M01(m)

M02(dd)

M07(m)

M06(m)

1.06

1.27

1.741.83

1.84

1.85

1.86

1.87

2.11

2.13

2.14

2.32

3.52

3.533.54

3.56

3.64

3.65

3.66

3.66

3.675.01

5.02

5.03

5.03

7.10

7.127.

137.

14

N

SO Me

S17


Acquisition Time (sec) 1.0912 Comment Date 15 Jun 2009 16:55:28Date Stamp 15 Jun 2009 16:55:28 File NameFrequency (MHz) 125.88 Nucleus 13C Number of Transients 256 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zgpg30Receiver Gain 7298.20 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 12587.9785 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000

3170-8-12f_011001r


21.0

123

.14

24.1

6

36.6

6

54.5

757

.45

76.8

077

.05

77.3

0

126.

4612

9.03

136.

09

141.

58N

SO Me

S18


Acquisition Time (sec) 3.1719 Comment 3170-13-p PROTON16 CDCl3 u dasso8 22 Date 16 Jun 2009 20:09:36Date Stamp 16 Jun 2009 20:09:36 File Name C:\Documents and Settings\leletra1\Desktop\sonia\3170-13-p_010001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zg30Receiver Gain 57.00 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3082.4949 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.06 (s, 9 H) 1.31 (s, 9 H) 1.71 - 1.92 (m, 3 H) 2.07 - 2.20 (m, 1 H) 3.45 - 3.54 (m, 1 H) 3.60 - 3.72 (m, 1 H) 5.02 (dd, J=8.04, 2.36 Hz, 1 H) 7.16 (d, J=8.20 Hz, 2 H) 7.31 (d, J=8.20 Hz, 2 H)3170-13-p_010001r


M08(s)

M09(s)

1.31

9.310.13.41.01.01.01.02.02.1

M01(d)

M02(d)

M05(m)M03(dd)

M04(m)

M06(m)

M07(m)

0.00

1.06

1.07

1.291.32

1.79

1.81

1.831.841.85

1.86

1.87

2.14

2.153.50

3.513.52

3.64

3.65

3.66

3.66

3.67

3.685.01

5.01

5.03

5.03

7.157.

177.

277.

307.

327.

34

N

SO

S19


Acquisition Time (sec) 1.0912 Comment 3170-13-p C13CPD2048 CDCl3 u dasso8 22 Date 17 Jun 2009 03:18:24Date Stamp 17 Jun 2009 03:18:24 File Name C:\Documents and Settings\leletra1\Desktop\sonia\3170-13-p_012001rFrequency (MHz) 125.88 Nucleus 13C Number of Transients 2048 Origin spectOriginal Points Count 32768 Owner nmrsu Points Count 32768 Pulse Sequence zgpg30Receiver Gain 13004.00 SW(cyclical) (Hz) 30030.03 Solvent CHLOROFORM-dSpectrum Offset (Hz) 14477.4912 Sweep Width (Hz) 30029.11 Temperature (degree C) 27.000

3170-13-p_012001r


23.1

824

.14

31.3

934

.40

36.4

9

54.1

057

.48

57.8

9

76.7

977

.04

77.2

9

125.

17126.

17

141.

28

149.

35

N

SO

S20


5/14/2009 3:26:28 PM


1H NMR (501 MHz, CHLOROFORM-d) δ ppm 0.86 - 1.06 (m, 2 H) 1.06 - 1.18 (m, 1 H) 1.14 - 1.31 (m, 11 H) 1.59 - 1.83 (m, 1 H) 3.11 - 3.25 (m, 1 H) 3.27 - 3.42 (m, 1 H) 3.50 - 3.64 (m, 1 H)


7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)

M05(m)

M06(m)

2.11.210.11.01.01.0

M03(m)M01(m)

M02(m)

M07(m)

M04(m)

0.00

0.950.97

0.98

1.00

1.101.13

1.20

7.28

N

SO

1.66

1.68

1.691.

731.

741.74

1.75

1.76

3.34

1.77

3.18

3.193.20

3.35

3.36

3.553.56

3.56

3.573.57

S21


5/14/2009 3:30:05 PM




23.4

926

.30

26.5

5

27.4

830

.73

41.5

7

50.0

657.5

9

62.7

3

76.7

777

.02

77.2

8

N

SO

S22


5/14/2009 3:46:41 PM


1H NMR (501 MHz, CHLOROFORM-d) δ ppm 0.96 (s, 9 H) 1.25 (s, 9 H) 1.70 - 1.93 (m, 4 H) 3.08 - 3.19 (m, 1 H) 3.28 - 3.38 (m, 1 H) 3.50 (dd, J=8.04, 4.26 Hz, 1 H)


7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

M05(s)

M06(s)

9.19.14.11.01.01.0

M01(dd)

M02(m)

M03(m)

M04(m)

0.90

0.96

1.23

1.27

1.76

1.771.

781.

781.

791.

831.

841.

861.

87

3.153.16

3.17

3.32

3.333.33

3.49

3.503.51

3.51

N

SO

S23


5/14/2009 3:51:36 PM




23.7

527

.02

27.4

0

35.8

5

48.2

8

58.7

5

68.3

0

76.8

677

.12

77.3

7

N

SO

S24


5/14/2009 3:57:25 PM


1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.18 (s, 9 H) 1.50 - 1.65 (m, 1 H) 1.67 - 1.79 (m, 1 H) 1.82 - 1.95 (m, 1 H) 2.02 (dd, J=11.98, 4.10 Hz, 1 H) 2.70 - 2.87 (m, 1 H) 3.71 - 3.81 (m, 1 H) 4.03 (q, J=7.36 Hz, 1 H) 5.06 (d, J=10.72 Hz, 1 H) 5.16 (d, J=17.02 Hz, 1 H) 5.59 - 5.76 (m, 1 H)


7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

M11(s)

1.18

9.51.11.11.11.11.11.11.01.01.0

M05(m)M02(d)

M03(d)

M07(dd)

M09(m)

M08(m)

M04(q)

M10(m)M06(m)M01(m)

7.31

N

SO

1.59

1.61

1.74

1.76

1.87

1.88

1.89

2.00

2.01

2.02

2.032.75

2.77

2.77

2.78

2.79

2.80

3.74

3.75

3.76

3.76

3.77

3.78

3.784.

024.

034.

055.05

5.07

5.155.18

5.63

5.65

5.655.67

5.68

5.69

5.70

S25


5/14/2009 4:01:45 PM




23.7

825

.79

32.6

0

41.2

6

57.0

1

67.9

3

76.8

177

.07

77.3

2

115.

73

140.

18

N

SO

S26


5/14/2009 1:56:05 PM

Acquisition Time (sec) 3.1719 Comment 3140-84-f PROTON16 CDCl3 u leletra1 10 Date 14 May 2009 13:07:12Date Stamp 14 May 2009 13:07:12 File Name \\phuseh-S1603\LELETRA1∴DATA\NMR data\3140-84-F_012001rFrequency (MHz) 500.63 Nucleus 1H Number of Transients 16 Origin spectOriginal Points Count 32768 Owner drinkdo1 Points Count 32768 Pulse Sequence zg30Receiver Gain 256.00 SW(cyclical) (Hz) 10330.58 Solvent CHLOROFORM-dSpectrum Offset (Hz) 3075.9272 Sweep Width (Hz) 10330.26 Temperature (degree C) 27.000

1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.61 - 1.73 (m, 1 H) 1.79 - 2.02 (m, 3 H) 2.14 - 2.24 (m, 1 H) 2.98 - 3.06 (m, 1 H) 3.17 - 3.25 (m, 1 H) 4.12 (t, J=7.72 Hz, 1 H) 7.18 - 7.27 (m, 2 H) 7.28 - 7.40 (m, 3 H)


10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

1.03.41.01.01.01.05.2

M03(t)M05(m)

M02(m)M04(m)

M06(m)

M08(m)

M01(m)

M07(m)

0.00

1.67

1.68

1.701.85

1.86

1.87

1.97

2.172.18

2.20

3.003.01

3.02

3.04

3.18

3.19

3.20

3.21

3.214.104.

124.

137.22

7.247.

257.

307.

31

7.35

7.37

NH

S27


5/14/2009 2:03:50 PM




25.5

834.2

9

46.9

4

62.5

776.8

177

.07

77.3

2

126.

5412

8.35

144.

66

NH

S28



1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.68 (m) 1.88 (m) 2.17 (m) 2.74 (br. s.) 2.99 (m) 3.18 (m) 4.09 (t, J=7.88 Hz) 7.28 (m)VerticalScaleFactor = 13140-84-R_010001r

9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 -0.5Chemical Shift (ppm)

1.12.21.01.61.01.01.05.2

M03(m)

M04(m)

M02(t)M06(m)

M08(m)

M05(br. s.)

M07(m)M01(m)

1.661.67

1.681.701.84

1.85

1.85

1.86

1.902.

172.

182.

742.

983.00

3.18

3.183.19

3.19

3.204.

084.

094.

11

7.20

7.227.29

7.307.34

7.35

NH

S29





25.5

3

34.2

0

46.8

6

62.6

0

76.8

677

.11

77.3

7

126.

5812

8.38

144.

34NH

S30


5/14/2009 2:16:12 PM


1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.50 - 1.64 (m, 1 H) 1.74 - 1.97 (m, 3 H) 2.09 - 2.21 (m, 1 H) 2.93 - 3.05 (m, 1 H) 3.11 - 3.20 (m, 1 H) 4.05 (t, J=7.72 Hz, 1 H) 7.22 (d, J=8.20 Hz, 2 H) 7.40 (d, J=8.51 Hz, 2 H)



1.03.01.01.01.01.02.01.9

M03(t)

M02(d)

M01(d)

M04(m)

M06(m)M05(m)

M08(m)

M07(m)

1.58

1.601.

811.

871.871.88

1.89

1.89

1.902.14

2.15

2.162.

982.

983.00

3.133.143.15

3.153.16

3.164.

044.

054.

07

7.22

7.23

7.40

7.41

NH

Br

S31


5/14/2009 2:21:19 PM



208 200 192 184 176 168 160 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 0Chemical Shift (ppm)

25.5

0

34.4

746.9

361.8

2

76.8

677

.11

77.3

6

120.

27

128.

2513

1.27

144.

17

NH

Br

S32



1H NMR (501 MHz, CHLOROFORM-d) δ ppm 1.59 (dd, J=12.30, 9.14 Hz) 1.85 (m) 2.16 (m) 2.99 (m) 3.15 (m) 4.05 (t, J=7.57 Hz) 7.22 (d, J=8.20 Hz) 7.41 (d, J=8.20 Hz)

VerticalScaleFactor = 1

3140-65-R_010001r

12.0 11.5 11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0Chemical Shift (ppm)

NH

Br

M01(d)

M02(d)

7.40

7.23

7.42

7.22

M05(m) M07(m)M03(t)

M04(m) M06(m) M08(dd)

4.05

1.02.12.11.01.02.1

4.07 4.04

3.16 3.

16 3.15

3.14

3.13 3.

002.

99 2.21

2.16 2.14

1.87 1.83

1.83 1.

821.

611.

59 1.59

S33





25.5

0

34.4

4

46.9

3

61.8

7

76.8

677

.12

77.3

7

120.

36

128.

2913

1.33

144.

02

NH

Br

S34

Leleti Rajender Reddy,* Mahavir Prashad

Documents

Transcript of Leleti Rajender Reddy,* Mahavir Prashad