Sodium hydride → HCID 14649985, compound

HRID 1721851Notes

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:21]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:24][CH:25]=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][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[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, 1.8 g) in 35 ml of dimethylformamide was treated with a solution of 9.00 g of 1-acetyl-4-hydroxy-4-phenylpiperidine in 100 ml of dimethylformamide and heated at 70° C. until evolution of gas had ceased. A solution of 7.38 g of 3-fluorobenzotrifluoride in 20 ml of dimethylformamide was added, dropwise, and the reaction allowed to proceed at 70° C. for 20 hours. The reaction mixture was then poured into an ice/water mixture 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 50% ethyl acetate/dichloromethane) afforded 3.11 g (20.90%) of 1-acetyl-4-phenyl-4-(3-trifluoromethylphenoxy)piperidine, m.p. 100°-103° C.

Workup

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
washHigh pressure liquid chromatography of the oil (silica gel; elution with 50% ethyl acetate/dichloromethane)

Sources & evidence

ORD record: ord-146d875aa3d048ac942755af437b8b16
Source dataset: uspto-grants-1989_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04853384

Reaction notes

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