Methyl 4-(3-bromopropyl)benzoate → 4-(3-{2-[4-Biphenyl-3-yl-3-(tert-butyl-dimethyl-silanyloxy)-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl ester

HRID 2219696Notes

Reaction equation

HRID 2219696 reaction equation
[C:1]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH:8]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:9][CH2:10][CH:11]2[NH:15][C:14](=[O:16])[CH2:13][CH2:12]2)[CH:2]=1.[CH3:31][O:32][C:33](=[O:44])[C:34]1[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][CH2:42]Br)=[CH:36][CH:35]=1>>[CH3:31][O:32][C:33](=[O:44])[C:34]1[CH:39]=[CH:38][C:37]([CH2:40][CH2:41][CH2:42][N:15]2[C:14](=[O:16])[CH2:13][CH2:12][CH:11]2[CH2:10][CH2:9][CH:8]([O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[CH2:7][C:3]2[CH:2]=[C:1]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH:6]=[CH:5][CH:4]=2)=[CH:36][CH:35]=1

Participants

3

Reactant 2

HCID 10801120Methyl 4-(3-bromopropyl)benzoateHCID 227124795-[4-Biphenyl-3-yl-3-(tert-butyl-dimethyl-silanyloxy)-butyl]-pyrrolidin-2-one

Product 1

HCID 692710644-(3-{2-[4-Biphenyl-3-yl-3-(tert-butyl-dimethyl-silanyloxy)-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl esterYield 74.2%

Procedure

Analogous to the procedure described for Compound 1A, Step D, 5-[4-biphenyl-3-yl-3-(tert-butyl-dimethyl-silanyloxy)-butyl]-pyrrolidin-2-one (5.116 g, 12.08 mmol) was alkylated with 4-(3-bromo-propyl)-benzoic acid methyl ester (3.41 g, 13.3 mmol) over 20 h. Purification by medium pressure chromatography using a solvent gradient (5:1 hexanes:EtOAc to 1:1 hexanes:EtOAc to EtOAc to 1% MeOH in CH2Cl2 to 5% MeOH in CH2Cl2) provided 4-(3-{2-[4-biphenyl-3-yl-3-(tert-butyl-dimethyl-silanyloxy)-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl ester (5.38 g). 1H NMR (CDCl3) δ 7.93 (d, 2H), 7.56 (d, 2H), 7.43 (m, 3H), 7.34 (m, 3H), 7.23 (m, 2H), 7.12 (m, 1H), 3.89 (m, 1H), 3.87 (s, 3H), 3.64 (m, 1H), 3.49 (m, 1H), 2.95-2.61 (m, 5H), 2.30 (m, 2H), 2.01 (m, 1H), 1.89-1.70 (m, 3H), 1.59-1.24 (m, 4H), 0.84 (s, 9H), −0.04 (d, 3H), −0.16 (d, 3H).

Workup

  1. customPurification by medium pressure chromatography

Sources & evidence

ORD record
ord-3698cbc8feb04454b5b33fc0a219c691
Source dataset
uspto-grants-2008_08
Patent number
US07414071B2

Reaction notes

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