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

HRID 1197473Notes

Reaction equation

HRID 1197473 reaction equation
[C:1]([N:4]1[CH2:12][CH2:11][CH:7]([C:8](Cl)=[O:9])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[Al+3].[Cl-].[Cl-].[Cl-].[F:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[CH:19]=1>>[F:17][C:18]1[CH:19]=[C:20]([F:24])[CH:21]=[CH:22][C:23]=1[C:8]([CH:7]1[CH2:11][CH2:12][N:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]1)=[O:9]

Participants

4

Reactant 3

HCID 97411,3-DifluorobenzeneHCID 1009501-Acetylpiperidine-4-carbonyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 27407071-Acetyl-4-(2',4'-difluorobenzoyl)piperidineYield 82.1%

Conditions

Temperature
25 °C

Procedure

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.

Workup

  1. temperatureThe mixture was then refluxed, under N2 for 4.5 hours
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted (2×100 ml CH2Cl2)
  4. dry with materialdried with MgSO4
  5. concentrationConcentration in vacuo

Sources & evidence

ORD record
ord-cfefbb53fbcc40a2aefbcacefd9e2518
Source dataset
uspto-grants-1994_01
Patent number
US05276040

Reaction notes

Loading…