1,4-Difluorobenzene → 1-Acetyl-4-(2,5-difluorobenzoyl)piperidine
Reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10](Cl)=[O:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[F:17][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=1>>[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10](=[O:11])[C:22]2[CH:23]=[C:18]([F:17])[CH:19]=[CH:20][C:21]=2[F:24])[CH2:6][CH2:5]1)(=[O:3])[CH3:2]Participants
Procedure
To a stirred suspension of 100 g of 1-acetyl-4-piperidine carboxylic acid chloride in 500 ml of 1,4-difluorobenzene was added in aliquots, 211 g of anhydrous aluminum chloride. The mixture was stirred at reflux under nitrogen for 3 hrs and allowed to cool to room temperature. The mixture was poured into ice and extracted twice with ethyl acetate. The extracts were washed with saturated sodium bicarbonate solution and dried over anhydrous potassium carbonate. Filtration followed by evaporation of the solvent provided an oil which crystallized on standing. The solid was washed with cyclohexane and dried to provide 73.3 g (52.1%) of 1-acetyl-4-(2,5 -difluorobenzoyl)-piperidine: mp 82°-87° C. Recrystallization from a mixture of isopropyl alcohol, diisopropyl ether and hexane provided product with mp 93°-95° C.
Workup
- temperatureat reflux under nitrogen for 3 hrs
- additionThe mixture was poured into ice
- extractionextracted twice with ethyl acetate
- washThe extracts were washed with saturated sodium bicarbonate solution
- dry with materialdried over anhydrous potassium carbonate
- filtrationFiltration
- customfollowed by evaporation of the solvent
- customprovided an oil which
- customcrystallized
- washThe solid was washed with cyclohexane
- customdried
Sources & evidence
- ORD record
- ord-6e359f1e3ea74139a7bf5a9c2f973868
- Source dataset
- uspto-grants-1989_05
- Patent number
- US04833244
Reaction notes
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