Anisole → 1-[4-(4-Methoxybenzoyl)piperidin-1-yl]ethan-1-one

HRID 1861772Notes

Reaction equation

HRID 1861772 reaction equation
[Cl-].[Cl-].[Cl-].[Al+3].[C:5]1([O:11][CH3:12])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[C:13]([N:16]1[CH2:24][CH2:23][CH:19]([C:20](Cl)=[O:21])[CH2:18][CH2:17]1)(=[O:15])[CH3:14]>C(=S)=S>[C:13]([N:16]1[CH2:17][CH2:18][CH:19]([C:20](=[O:21])[C:8]2[CH:9]=[CH:10][C:5]([O:11][CH3:12])=[CH:6][CH:7]=2)[CH2:23][CH2:24]1)(=[O:15])[CH3:14]

Participants

5

Reactant 3

HCID 7519AnisoleHCID 1009501-Acetylpiperidine-4-carbonyl chlorideHCID 6451240Aluminum(III) Chloride

Product 1

HCID 186215481-[4-(4-Methoxybenzoyl)piperidin-1-yl]ethan-1-oneYield 60%

Reagents, catalysts & solvents 1

HCID 6348Carbon DisulfideSolvent

Procedure

To a suspension of aluminum trichloride (3.40 g, 25.7 mmol) in CS2 (15 mL) were added anisole (1.90 mL, 17.6 mmol) and, portionwise, N-acetylisonipecotoyl chloride (2.40 g, 11.7 mmol). After the addition was complete, the mixture was refluxed for 1 h. The solvent was decanted and the red residue was dissolved in 5% HCl (50 mL) and was extracted with EtOAc (4×30 mL). The combined organic phase was dried and was concentrated under reduced pressure to afford the title compound as a colorless solid (1.8 g, 60%): mp 102-105° C.; 1H NMR (CDCl3) d 1.50-1.75 (m, 1H), 1.70-2.00 (m, 3H), 2.10 (s, 3H), 2.70-2.90 (m, 1H), 3.15-3.30 (m, 1H), 3.40-3.53 (m, 1H), 3.86 (s, 3H), 3.85-4.00 (m, 1H), 4.56 (d, J=13.2 Hz, 1H), 6.94 (d, J=8.7 Hz, 2H), 7.92 (d, J=9.0 Hz, 2H).

Workup

  1. additionAfter the addition
  2. temperaturethe mixture was refluxed for 1 h
  3. customThe solvent was decanted
  4. dissolutionthe red residue was dissolved in 5% HCl (50 mL)
  5. extractionwas extracted with EtOAc (4×30 mL)
  6. customThe combined organic phase was dried
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-e965867d104f432e8da9d21668e84444
Source dataset
uspto-grants-2003_03
Patent number
US06534522B2

Reaction notes

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