Sodium Bicarbonate → Tert-butyl 2-phenyl-4-{[trans-2-(4-{[3-(trifluoromethyl)benzoyl]amino}phenyl)cyclopropyl]amino}-piperidine-1-carboxylate

HRID 922538Notes

Reaction equation

HRID 922538 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:5][C@H:4]1[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)=[CH:8][CH:7]=1.O=[C:26]1[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:28]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH2:27]1.C(=O)([O-])O.[Na+].[BH4-].[Na+]>CO.C1COCC1>[C:39]1([CH:28]2[CH2:27][CH:26]([NH:2][C@@H:3]3[CH2:5][C@H:4]3[C:6]3[CH:7]=[CH:8][C:9]([NH:12][C:13](=[O:24])[C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:22])([F:23])[F:21])[CH:15]=4)=[CH:10][CH:11]=3)[CH2:31][CH2:30][N:29]2[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

7

Reactant 4

HCID 516892Sodium Bicarbonate2×HCID 4311764Sodium borohydrideHCID 445586011-Boc-2-phenyl-piperidin-4-oneHCID 86729839N-[4-(trans-2-aminocyclopropyl)phenyl]-3-(trifluoromethyl)benzamide hydrochloride

Product 1

HCID 86729901Tert-butyl 2-phenyl-4-{[trans-2-(4-{[3-(trifluoromethyl)benzoyl]amino}phenyl)cyclopropyl]amino}-piperidine-1-carboxylateYield 63.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of N-[4-(trans-2-aminocyclopropyl)phenyl]-3-(trifluoromethyl)benzamide hydrochloride (60 mg) in methanol (1.5 mL)/THF (1.5 mL) were added tert-butyl 4-oxo-2-phenylpiperidine-1-carboxylate (60.2 mg) and sodium hydrogen carbonate (28.3 mg). The mixture was stirred at 60° C. for 1 hr, and ice-cooled to 0° C. and sodium borohydride (12.7 mg) was added. The mixture was stirred at room temperature for 2 hr, and ice-cooled to 0° C. and saturated aqueous sodium hydrogen carbonate solution was added. The mixture was extracted with ethyl acetate, and the extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/methanol) to give the title compound (62 mg).

Workup

  1. temperatureice-cooled to 0° C.
  2. stirringThe mixture was stirred at room temperature for 2 hr
  3. temperatureice-cooled to 0° C.
  4. extractionThe mixture was extracted with ethyl acetate
  5. washthe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol)

Sources & evidence

ORD record
ord-c8c47b76443b458c8698bad9fb5cbd83
Source dataset
uspto-grants-2016_03
Patent number
US09278931B2

Reaction notes

Loading…