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

HRID 458987Notes

Reaction equation

HRID 458987 reaction equation
[C:1]([Si:5]([CH3:25])([CH3:24])[O:6][CH:7]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH2:8][CH2:9][CH:10]1[NH:14][C:13](=[O:15])[CH2:12][CH2:11]1)([CH3:4])([CH3:3])[CH3:2].[CH3:26][O:27][C:28](=[O:39])[C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][CH2:37]Br)=[CH:31][CH:30]=1>>[CH3:26][O:27][C:28](=[O:39])[C:29]1[CH:34]=[CH:33][C:32]([CH2:35][CH2:36][CH2:37][N:14]2[C:13](=[O:15])[CH2:12][CH2:11][CH:10]2[CH2:9][CH2:8][CH:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:25])[CH3:24])[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[CH:31][CH:30]=1

Participants

3

Reactant 2

HCID 10801120Methyl 4-(3-bromopropyl)benzoateHCID 227125205-[3-(Tert-butyl-dimethyl-silanyloxy)4-(4-fluoro-phenyl)-butyl]-pyrrolidin-2-one

Product 1

HCID 692689634-(3-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-(4-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl esterYield 57%

Procedure

Analogous to the procedure described for Example 1A, Step D, 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-(4-fluoro-phenyl)-butyl]-pyrrolidin-2-one (296 mg, 0.809 mmol) was alkylated with 4-(3-bromo-propyl)-benzoic acid methyl ester (276 mg, 1.07 mmol) over 72 h. Purification by medium pressure chromatography (1:1 hexanes:EtOAc) provided 4-(3-{2-[3-(tert-butyl-dimethyl-silanyloxy)-4-(4-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-propyl)-benzoic acid methyl ester (250 mg). 1H NMR (CDCl3) (selected peaks) δ7.92 (d, 2H), 7.21 (d, 2H), 7.05 (m, 2H), 6.92 (m, 2H), 3.86 (s, 3H), 3.76 (m, 1H), 3.62 (m, 1H), 3.45 (m, 1H), 0.81 (s, 9H).

Workup

  1. customPurification by medium pressure chromatography (1:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-d299f5144ae645b3a18a0e80be1e7299
Source dataset
uspto-grants-2007_03
Patent number
US07192979B2

Reaction notes

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