Potassium Carbonate → (3R*,4R*)-1-[(1-acetylpiperidin-4-yl)carbonyl]-3-(3,4-dichlorophenyl)-N-methylpiperidin-4-amine

HRID 2047436Notes

Reaction equation

HRID 2047436 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]([N:12]2[CH2:17][CH2:16][C@@H:15]([N:18](C)[C:19](=O)C(F)(F)F)[C@H:14]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=3)[CH2:13]2)=[O:11])[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+]>CO.O>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([C:10]([N:12]2[CH2:17][CH2:16][C@@H:15]([NH:18][CH3:19])[C@H:14]([C:26]3[CH:31]=[CH:30][C:29]([Cl:32])=[C:28]([Cl:33])[CH:27]=3)[CH2:13]2)=[O:11])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 11430Potassium Carbonate2×HCID 57741667rel-N-[(3R,4R)-1-[(1-Acetyl-4-piperidinyl)carbonyl]-3-(3,4-dichlorophenyl)-4-piperidinyl]-2,2,2-trifluoro-N-methylacetamide

Product 1

HCID 57741761(3R*,4R*)-1-[(1-acetylpiperidin-4-yl)carbonyl]-3-(3,4-dichlorophenyl)-N-methylpiperidin-4-amineYield 58%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

To a mixed solution of the compound (0.66 g) obtained in step 4 in methanol (6.5 mL) and water (1.3 mL) was added potassium carbonate (0.35 g) at room temperature, and the mixture was stirred at 50° C. for 24 hr. Furthermore, potassium carbonate (1.70 g) was added, and the mixture was stirred at 50° C. for 6 days. The organic solvent was evaporated under reduced pressure, and the residue was poured into saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic layer was washed with saturated brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 0→9% methanol/ethyl acetate) to give the title compound (0.30 g, 58%) as a white amorphous solid.

Workup

  1. stirringthe mixture was stirred at 50° C. for 6 days
  2. customThe organic solvent was evaporated under reduced pressure
  3. additionthe residue was poured into saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. customdried
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 0→9% methanol/ethyl acetate)

Sources & evidence

ORD record
ord-ad22189badbd4a01841e7b78669e3d23
Source dataset
uspto-grants-2013_11
Patent number
US08592454B2

Reaction notes

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