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 352594Notes

Reaction equation

HRID 352594 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 Example 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) δ7.93 (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-abec564d4f9e4bcf8baf8e267a1e05b3
Source dataset
uspto-grants-2004_06
Patent number
US06747054B2

Reaction notes

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