Sodium hydride → HCID 14649984, compound

HRID 1721850Notes

Reaction equation

[H-].[Na+].[C:3]([N:6]1[CH2:11][CH2:10][C:9]([OH:18])([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:8][CH2:7]1)(=[O:5])[CH3:4].F[C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1>CN(C)C=O>[C:3]([N:6]1[CH2:11][CH2:10][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)([O:18][C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=2)[CH2:8][CH2:7]1)(=[O:5])[CH3:4]

Participants

Conditions

Temperature: 70 °C

Procedure

A stirred suspension of sodium hydride (60% in oil, 2.0 g) in 50 ml of dimethylformamide was treated with a solution of 9.8 g of 1-acetyl-4-hydroxy-4-phenylpiperidine in 80 ml of dimethylformamide and then heated at 70° C. for 1 hour. After cooling to room temperature a solution of 8.06 g of 4-fluorobenzotrifluoride in 20 ml of dimethylformamide was added dropwise and the reaction allowed to proceed for 25 hours. The reaction mixture was then poured into 400 ml of ice water and the aqueous suspension extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated to an oil. High pressure liquid chromatography of the oil (silica gel; elution with a 10% solution of ethyl acetate in dichloromethane) afforded 5.3 g of 1-acetyl-4-phenyl-4-(4-trifluoromethylphenoxy)piperidine, m.p. 96°-100° C.

Workup

additionwas added dropwise
extractionthe aqueous suspension extracted with ethyl acetate
washThe organic layer was washed with water
dry with materialdried over anhydrous magnesium sulfate
filtrationfiltered
concentrationconcentrated to an oil
washelution with a 10% solution of ethyl acetate in dichloromethane)

Sources & evidence

ORD record: ord-6748d889321d4d3a9a38a89360b682d2
Source dataset: uspto-grants-1989_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04853384

Reaction notes

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