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

HRID 1582664Notes

Reaction equation

HRID 1582664 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-38487e3b47ae4fa58a49dc8baaa7533e
Source dataset
uspto-grants-2004_05
Patent number
US06737437B2

Reaction notes

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