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

HRID 478859Notes

Reaction equation

HRID 478859 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].[H-].[Na+].Br[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]#[N:36].O>CN(C=O)C>[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[CH2:11][CH2:12][C:13](=[O:15])[N:14]1[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][C:35]#[N:36])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 88737Heptanenitrile, 7-bromo-HCID 227125205-[3-(Tert-butyl-dimethyl-silanyloxy)4-(4-fluoro-phenyl)-butyl]-pyrrolidin-2-one

Product 1

HCID 227187687-{2-[3-(Tert-butyl-dimethyl-silanyloxy)-4-(4-fluoro-phenyl)-butyl]-5-oxo-pyrrolidin-1-yl}-heptanenitrileYield 82.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
90 °C

Procedure

A solution o f 5-[3-(tert-butyl-dimethyl-silanyloxy)4-(4-fluoro-phenyl)-butyl]-pyrrolidin-2-one (150 mg, 0.41 mmol) in DMF (5 mL) was added to NaH (60% by weight in oil, 16 mg, 0.41 mmol) in DMF (10 mL). After 1.5 h, 7-bromoheptanenitrile (78 mg, 0.41 mmol) in DMF (5 mL) was added and the reaction mixture was stirred at 90° C. for 2.5 h. Water (20 mL) was added and the aqueous solution was washed with EtOAc (4×15 mL). The combined organic solutions were washed with water (2×15 mL), dried (MgSO4), filtered, and concentrated. The residue was purified by medium pressure chromatography (1:1 hexanes:EtOAc) provided 7-{2-[3-(tert-butyl-dimethyl-silanyloxy)-4-(4-fluoro-phenyl)-butyl ]-5-oxo-pyrrolidin-1-yl}-heptanenitrile (161 mg). 1H NMR (CDCl3) δ7.09 (m, 2H), 6.95 (m, 2H), 3.81 (m, 1H), 3.54 (m, 2H), 2.86 (m, 1H), 2.68 (m, 2H), 2.29 (m, 4H), 2.06 (m, 1H), 1.74-1.23 (m, 13H), 0.85 (s, 9H), 0.04 (m, 3H), 0.19 (m, 3H); MS 475.1 (M+1).

Workup

  1. washthe aqueous solution was washed with EtOAc (4×15 mL)
  2. washThe combined organic solutions were washed with water (2×15 mL)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by medium pressure chromatography (1:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-e30f3d930ef34898850a8b6db3d9c81f
Source dataset
uspto-grants-2003_11
Patent number
US06642266B2

Reaction notes

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