Fluorobenzene → 1-Acetyl-3-(4-fluorobenzoyl)piperidine
Reaction equation
S(Cl)(Cl)=O.[C:5]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([OH:16])=O)[CH2:9]1)(=[O:7])[CH3:6].[Cl-].[Al+3].[Cl-].[Cl-].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[C:5]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]([C:25]2[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=2)=[O:16])[CH2:9]1)(=[O:7])[CH3:6]Participants
5
Procedure
Thionyl chloride (2.12 ml, 32.1 mmol) was added to fluorobenzene solution (20 ml) of 1-acetyl-3-piperidinecarboxylic acid (5.00 g, 29.2 mmol) under ice-cooling, which was stirred at room temperature for 30 minutes. Aluminum chloride (9.74 g, 73.0 mmol) was added to the solution, which was stirred at 90° C. for 1 hour. The reaction mixture was poured in ice, and extraction was conducted using ethyl acetate. The extract was washed with saturated aqueous sodium chloride solution, saturated sodium hydrogencarbonate solution, and again saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then the solvent was distilled out under reduced pressure. The resulting oily substance was purified by silica gel column chromatography (development solvent; hexane:ethyl acetate=1:1), to give (1-acetyl-3-piperidinyl)(4-fluorophenyl)methanone (4.93 g).