Sodium bis(trimethylsilyl)amide → 4-(2-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-ethoxy)-benzoic acid ethyl ester

HRID 458989Notes

Reaction equation

HRID 458989 reaction equation
[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][CH:7]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[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].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:35]([O:37][C:38](=[O:49])[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH2:47]Br)=[CH:41][CH:40]=1)[CH3:36]>>[CH2:35]([O:37][C:38](=[O:49])[C:39]1[CH:44]=[CH:43][C:42]([O:45][CH2:46][CH2:47][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]([CH3:3])([CH3:2])[CH3:4])([CH3:24])[CH3:23])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:41][CH:40]=1)[CH3:36]

Participants

4

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 12708668Ethyl 4-(2-bromoethoxy)benzoateHCID 129700855-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one

Product 1

HCID 692713194-(2-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-ethoxy)-benzoic acid ethyl esterYield 17.1%

Conditions

Temperature
50 °C

Procedure

Analogous to the procedure described for Example 1A, Step D, 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-pyrrolidin-2-one (prepared in Example 1A, Step C) (250 mg, 0.719 mmol) was alkylated with NaHMDS (1 M in THF, 0.86 mL, 0.86 mmol) and 4-(2-bromo-ethoxy)-benzoic acid ethyl ester (216 mg, 0.791 mmol). The reaction temperature was maintained at 50° C. over 24 h. Purification by radial chromatography (hexanes to 4:1 hexanes:EtOAc) provided 4-(2-{2-[3-(tert-butyl-dimethyl-silanyloxy)-4-phenyl-butyl]-5-oxo-pyrrolidin-1-yl}-ethoxy)-benzoic acid ethyl ester (66.4 mg). 1H NMR (CDCl3) (selected peaks) δ7.96 (m, 2H), 7.29–7.13 (m, 5H), 6.84 (m, 2H), 4.33 (q, 2H), 4.12 (m, 2H), 3.90 (m, 2H), 3.68 (m, 1H), 3.34 (m, 1H), 2.73 (m, 2H), 2.32 (m, 2H), 1.36 (t, 3H), 0.85 (s, 9H), −0.03 (s, 3H), −0.15 (d, 3H).

Workup

  1. customPurification by radial chromatography (hexanes to 4:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-03cc8268810b49b4a3121dfe2970cc10
Source dataset
uspto-grants-2007_03
Patent number
US07192979B2

Reaction notes

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