Water → N-[(3R,4R)-1-[(1-acetylpiperidin-4-yl)methyl]-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-chloro-N-methylbenzamide

HRID 1260971Notes

Reaction equation

HRID 1260971 reaction equation
Cl.[Cl:2][C:3]1[CH:33]=[CH:32][C:6]([C:7]([N:9]([C@@H:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[CH2:13][C@H:12]2[C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=2)[CH3:10])=[O:8])=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:41](Cl)(=[O:43])[CH3:42].O>C1COCC1>[C:41]([N:21]1[CH2:22][CH2:23][CH:18]([CH2:17][N:14]2[CH2:15][CH2:16][C@@H:11]([N:9]([CH3:10])[C:7](=[O:8])[C:6]3[CH:5]=[CH:4][C:3]([Cl:2])=[CH:33][CH:32]=3)[C@H:12]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([Cl:31])[CH:25]=3)[CH2:13]2)[CH2:19][CH2:20]1)(=[O:43])[CH3:42]

Participants

6

Reactant 4

HCID 962WaterHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 689301854-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-(piperidin-4-ylmethyl)piperidin-4-yl]-N-methylbenzamide Monohydrochloride

Product 1

HCID 68870199N-[(3R,4R)-1-[(1-acetylpiperidin-4-yl)methyl]-3-(3,4-dichlorophenyl)piperidin-4-yl]-4-chloro-N-methylbenzamideYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 4-chloro-N-[(3R,4R)-3-(3,4-dichlorophenyl)-1-(piperidin-4-ylmethyl)piperidin-4-yl]-N-methylbenzamide monohydrochloride (100 mg) obtained in Example 463 and triethylamine (78 μL) in THF (3 mL) was added acetyl chloride (40 μL) at room temperature, and the mixture was stirred for 14 hr. To the reaction mixture was added water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound (12.5 mg, 12%) as a white powder.

Workup

  1. extractionthe resultant product was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution and brine
  3. customdried
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-815f9ae8c681487bbf39c180a76503dd
Source dataset
uspto-grants-2013_06
Patent number
US08470816B2

Reaction notes

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