Heptanenitrile, 7-bromo- → 7-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-(3-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile

HRID 478863Notes

Reaction equation

HRID 478863 reaction equation
[C:1]([Si:5]([CH3:25])([CH3:24])[O:6][CH:7]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[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+].Br[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]#[N:44]>>[C:1]([Si:5]([CH3:25])([CH3:24])[O:6][CH:7]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[CH:18]=1)[CH2:8][CH2:9][CH:10]1[CH2:11][CH2:12][C:13](=[O:15])[N:14]1[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][C:43]#[N:44])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 3

HCID 88737Heptanenitrile, 7-bromo-HCID 2724254Sodium bis(trimethylsilyl)amideHCID 129700955-[3-(Tert-butyldimethyl-silanyloxy)-4-(3-fluoro-phenyl)-butyl]-pyrrolidin-2-one

Product 1

HCID 227187587-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-(3-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrileYield 80.6%

Procedure

Following the procedure described for Example 5, Step A, the anion derived 5-[3-(tert-butyl-dimethyl-silanyloxy)-4-(3-fluoro-phenyl)-butyl]-pyrrolidin-2-one (250 mg, 0.684 mmol) and NaHMDS (1M in THF, 0.80 mL, 0.80 mmol) was alkylated with 7-bromoheptanenitrile (142 mg, 0.748 mmol) at 70° C. for 72 h. Purification by medium pressure chromatography (1:1 hexanes:EtOAc to EtOAc to 5% MeOH in CH2Cl2) provided 7-{2-[3-(tert-butyl-dimethyl-silanyloxy)-4-(3-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrile (261.7 mg). 1H NMR (CDCl3) δ7.26 (m, 1H), 6.92 (m, 3H), 3.89 (m, 1H), 3.59 (m, 2H), 2.89 (m, 1H), 2.75 (m, 2H), 2.36 (m, 4H), 2.11 (m, 1H), 1.72-1.26 (m, 13H), 0.89 (s, 9H), 0.09 (s, 6H); MS 475.3 (M+1).

Workup

  1. customPurification by medium pressure chromatography (1:1 hexanes:EtOAc to EtOAc to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-908762701dc048e2bdb0a02712c19dd0
Source dataset
uspto-grants-2003_11
Patent number
US06642266B2

Reaction notes

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