Hydrochloric Acid → 1-Benzoyl-4-(2,4-difluorobenzoyl)piperidine

HRID 1784720Notes

Reaction equation

[C:1]([N:9]1[CH2:14][CH2:13][CH:12]([C:15]([OH:17])=O)[CH2:11][CH2:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][CH:24]=1.[Cl-].[Al+3].[Cl-].[Cl-].Cl>ClCCl>[C:1]([N:9]1[CH2:10][CH2:11][CH:12]([C:15](=[O:17])[C:26]2[CH:25]=[CH:24][C:23]([F:22])=[CH:28][C:27]=2[F:29])[CH2:13][CH2:14]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 1-benzoylpiperidine-4-carboxylic acid (66 g, 285 mmol) in dichloromethane (160 mL) was added thionyl chloride (26 mL, 388 mmol). After stirring at 60° C. for 1 h, the mixture was added portionwise to a stirred suspension of 2,4-difluorobenzene (45 g, 397 mmol) and anhydrous aluminum chloride (88 g, 666 mmol) in dichloromethane (245 mL), and the reaction mixture was refluxed for 5 h. The reaction mixture was poured into a mixture of ice and concentrated hydrochloric acid and extracted with chloroform. The organic layer was dried over sodium sulfate and the solvent was evaporated under reduced pressure. Recrystallization from hexane gave 1-benzoyl-4-(2,4-difluorobenzoyl)piperidine (46 g, 50%) as colorless crystals.

Workup

temperaturethe reaction mixture was refluxed for 5 h
extractionextracted with chloroform
dry with materialThe organic layer was dried over sodium sulfate
customthe solvent was evaporated under reduced pressure
customRecrystallization from hexane

Sources & evidence

ORD record: ord-e86ce32564d64cb9b307b22e1e227e9e
Source dataset: uspto-grants-2009_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07504411B2

Reaction notes

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