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 1481817Notes

Reaction equation

HRID 1481817 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C@H:8]2[C@@H:13]([CH3:14])[N:12]([CH2:15][C:16]([F:19])([F:18])[F:17])[C:11](=[O:20])[C@@H:10]([NH:21]C(=O)OC(C)(C)C)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1>CO.[OH-].[OH-].[Pd+2]>[NH2:21][C@H:10]1[CH2:9][C@@H:8]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:2][CH:3]=2)[C@@H:13]([CH3:14])[N:12]([CH2:15][C:16]([F:17])([F:18])[F:19])[C:11]1=[O:20]

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 a pad of 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 a pad of 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-42217ccdac26411fbd4b90abec992f10
Source dataset
uspto-grants-2016_08
Patent number
US09409916B2

Reaction notes

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