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

HRID 1582659Notes

Reaction equation

HRID 1582659 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 of 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-ba8fb9dd310a43db8452a15782c381c0
Source dataset
uspto-grants-2004_05
Patent number
US06737437B2

Reaction notes

Loading…