Sodium hydride → Ethyl 3-(3,4-difluorobenzyl)-2-oxopiperidine-3-carboxylate

HRID 71144

Reaction equation

[O:1]=[C:2]1[CH:7]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][NH:3]1.[H-].[Na+].Br[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[C:19]([F:24])[CH:18]=1>CN(C=O)C.C(OCC)(=O)C.[Cl-].[NH4+]>[F:24][C:19]1[CH:18]=[C:17]([CH:22]=[CH:21][C:20]=1[F:23])[CH2:16][C:7]1([C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:6][CH2:5][CH2:4][NH:3][C:2]1=[O:1]

Participants

Conditions

Temperature: 0 °C

Procedure

Under a nitrogen atmosphere, to a mixture of ethyl 2-oxopiperidine-3-carboxylate (2.0 g) in DMF (20 mL) was added sodium hydride (60%, 0.47 g) at 0° C., and the mixture was stirred at 0° C. for 30 min. 4-(Bromomethyl)-1,2-difluorobenzene (1.50 mL) was added to the reaction mixture, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and saturated aqueous ammonium chloride solution, the mixture was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.82 g).

Workup

stirringthe mixture was stirred at room temperature overnight
washthe mixture was washed with saturated brine
dry with materialdried over anhydrous magnesium sulfate
customthe solvent was evaporated under reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record: ord-6984390e460d42cfaf5e95d0ceef91d0
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822699B2

Linked notes

Loading…