Triethylamine → 1-[2,4-Bis(trifluoromethyl)benzyl]-4-(hydroxymethyl)piperidin-2-one

HRID 1620603Notes

Reaction equation

[F:1][C:2]([F:25])([F:24])[C:3]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([C:12](O)=[O:13])[CH2:8][C:7]1=[O:15].C(N(CC)CC)C.ClC(OCC)=O.[BH4-].[Na+]>O1CCCC1.O>[F:25][C:2]([F:1])([F:24])[C:3]1[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH2:12][OH:13])[CH2:8][C:7]1=[O:15]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 1-[2,4-bis(trifluoromethyl)benzyl]-2-oxopiperidine-4-carboxylic acid (16.8 g) and triethylamine (9.8 mL) in tetrahydrofuran (200 mL) was added ethyl chloroformate (8.0 mL) under cooling to 0° C. under a nitrogen atmosphere. The reaction mixture was stirred for 1 hr under cooling to 0° C., sodium borohydride (5.18 g) was added, and the mixture was further stirred at 30° C. overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (10.9 g).

Workup

temperatureunder cooling to 0° C.
stirringthe mixture was further stirred at 30° C. overnight
extractionthe mixture was extracted with ethyl acetate
washThe extract was washed with saturated brine
dry with materialdried over sodium sulfate
customthe solvent was evaporated under reduced pressure
customThe residue was purified by silica gel column chromatography (ethyl acetate/petroleum ether)

Sources & evidence

ORD record: ord-985be7839fce482db320661b9f863cce
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772277B2

Reaction notes

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