1,3-Difluorobenzene → 1-Acetyl-4-(2',4'-difluorobenzoyl)piperidine

Participants

Reaction Conditions

Reaction Steps

N-Acetyl isonipecotoyl chloride (70.0 g, 0.369 mol) was added over a 20 minute period to a vigorously stirred suspension of AlCl3 (98 g, 0.735 mol) in 1,3-difluorobenzene (125 ml, 1.27 mol, Aldrich Chem. Co.) at 25° C. The mixture was then refluxed, under N2 for 4.5 hours, cooled to 25° C., and poured over 300 ml of ice/water. The layers were separated, the aqueous layer was extracted (2×100 ml CH2Cl2) and combined with the organic layer and dried with MgSO4. Concentration in vacuo gave 4-(2,4-difluorobenzoyl)-1-acetyl-piperidine (II) as a white solid (81 g, 82%), m.p. 94°-96° C.

Provenance & Evidence