tert-Butyl [(3S,5S,6R)-5-(3-chlorophenyl)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate → (3S,5S,6R)-3-Amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one

HRID 1404483Notes

Reaction equation

HRID 1404483 reaction equation
C(OC(=O)[NH:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16](Cl)[CH:15]=2)[C@@H:11]([CH3:21])[N:10]([CH2:22][C:23]([F:26])([F:25])[F:24])[C:9]1=[O:27])(C)(C)C>CO.[OH-].[OH-].[Pd+2]>[NH2:7][C@H:8]1[CH2:13][C@@H:12]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C@@H:11]([CH3:21])[N:10]([CH2:22][C:23]([F:24])([F:25])[F:26])[C:9]1=[O:27]

Participants

4

Reactant 1

HCID 86665193tert-Butyl [(3S,5S,6R)-5-(3-chlorophenyl)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate

Product 1

HCID 68749752(3S,5S,6R)-3-Amino-6-methyl-5-phenyl-1-(2,2,2-trifluoroethyl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Conditions

Temperature
23 °C

Procedure

A mixture of tert-butyl[(3S,5S,6R)-5-(3-chlorophenyl)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)piperidin-3-yl]carbamate (2.75 g, 6.53 mmol) and 20 wt. % palladium hydroxide on carbon (−50 wt. % wet, 700 mg, 0.50 mmol) in methanol (100 mL) was stirred under a hydrogen balloon at 23° C. for 16 h. The catalyst was removed by filtration through Celite® and washed thoroughly with methanol and ethyl acetate. Following concentration of the filtrate, a solution of the residue in ethyl acetate (100 mL) pre-cooled to 0° C. was sparged with HCl gas for ˜1 min. The ice-bath was removed and the acidic solution was allowed to warm to 23° C. as stirring was continued for 2 h. The mixture was then concentrated to dryness to afford the title compound as a hydrochloride salt. HRMS: m/z=287.1361, calculated m/z=287.1366 for C14H18F3N2O. 1H NMR (500 MHz, CD3OD) δ 7.39 (t, 2H, J=7.3 Hz), 7.31 (t, 1H, J=7.3 Hz), 7.27 (d, 2H, J=7.3 Hz), 4.81-4.73 (m, 1H), 4.24 (dd, 1H, J=12.0, 6.8 Hz), 3.94 (p, 1H, J=6.0 Hz), 3.76-3.67 (m, 2H), 2.56 (q, 1H, J=12.7 Hz), 2.42 (m, 1H), 1.00 (d, 3H, J=6.3 Hz).

Workup

  1. customThe catalyst was removed by filtration through Celite®
  2. washwashed thoroughly with methanol and ethyl acetate
  3. temperaturea solution of the residue in ethyl acetate (100 mL) pre-cooled to 0° C.
  4. customwas sparged with HCl gas for ˜1 min
  5. customThe ice-bath was removed
  6. temperatureto warm to 23° C.
  7. stirringas stirring
  8. waitwas continued for 2 h
  9. concentrationThe mixture was then concentrated to dryness

Sources & evidence

ORD record
ord-e2bfed87a0d74fef98b909c1955f1f64
Source dataset
uspto-grants-2014_12
Patent number
US08912210B2

Reaction notes

Loading…