Fluorobenzene → 1-Acetyl-4-(4-fluorobenzoyl)piperidine

HRID 324547

Reaction equation

HRID 324547 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].[Cl-].[Cl-].[Cl-].[Al+3].[F:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[F:17][C:18]1[CH:23]=[CH:22][C:21]([C:8]([CH:7]2[CH2:11][CH2:12][N:4]([C:1](=[O:3])[CH3:2])[CH2:5][CH2:6]2)=[O:9])=[CH:20][CH:19]=1

Participants

4

Reactant 3

HCID 10008FluorobenzeneHCID 1009501-Acetylpiperidine-4-carbonyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 1172571-Acetyl-4-(4-fluorobenzoyl)piperidineYield 50%

Procedure

N-acetyl-isonipecotic acid chloride (2.0 g, 10.5 mmol) was slowly added to a stirring mixture of aluminum trichloride (2.8 g, 21.1 mmol) in fluorobenzene (10 mL). After the addition was completed, the mixture was refluxed for 1 h. The mixture was poured into ice and the resulting layers were separated. The aqueous layer was extracted twice with CH2Cl2 (2×30 mL) and the combined organic phase was dried and concentrated under reduced pressure to afford the title compound as an oil (1.3 g, 50%). 1H NMR (CDCl3): 1.5-1.7 (m, 1H), 1.7-2.0 (m, 3H), 2.104 (s, 3H), 2.813 (t, J=12.0 Hz, 1H), 3.15-3.3 (m, 1H), 3.4-3.55 (m, 1H), 3.902 (d, J=13.2 Hz, 1H), 4.574 (d, J=13.2 Hz, 1H), 7.145 (t, J=8.4 Hz, 2H), 7.967 (dd, J=5.7 & 8.4 Hz, 2H).

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was refluxed for 1 h
  3. additionThe mixture was poured into ice
  4. customthe resulting layers were separated
  5. extractionThe aqueous layer was extracted twice with CH2Cl2 (2×30 mL)
  6. customthe combined organic phase was dried
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-e1c360238e73494db146d6bd6033559c
Source dataset
uspto-grants-2001_04
Patent number
US06218404B1

Linked notes

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