Hydrochloric Acid → (3S,5S,6R)-3-amino-5-(2-fluoro-3-methylphenyl)-6-methyl-1-(2,2,2-trifluoroethyl)piperidin-2-one

HRID 448216Notes

Reaction equation

HRID 448216 reaction equation
[F:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([N+:22]([O-])=O)[C:12](=[O:21])[N:13]([CH2:16][C:17]([F:20])([F:19])[F:18])[C:14]=1[CH3:15].Cl.[H][H]>CO.[Pt](=O)=O>[NH2:22][C@H:11]1[CH2:10][C@@H:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([CH3:8])[C:2]=2[F:1])[C@@H:14]([CH3:15])[N:13]([CH2:16][C:17]([F:19])([F:18])[F:20])[C:12]1=[O:21]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 86665195HCID 86665195, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 68748739(3S,5S,6R)-3-amino-5-(2-fluoro-3-methylphenyl)-6-methyl-1-(2,2,2-trifluoroethyl)piperidin-2-one

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 887MethanolSolvent

Procedure

A mixture of 5-(2-fluoro-3-methylphenyl)-6-methyl-3-nitro-1-(2,2,2-trifluoroethyl)pyridin-2(1H)-one (1.95 g, 5.66 mmol), platinum(IV) oxide (0.643 g, 2.83 mmol), and concentrated aqueous hydrochloric acid solution (12 M, 4.72 mL, 56.6 mmol) in methanol (57 mL) was shaken under 50 psi of hydrogen at 23° C. for 5 h. The catalyst was removed by filtration through Celite® and washed thoroughly with methanol. The filtrate was concentrated, and the residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was washed with brine, dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with dichloromethane initially, grading to 5% MeOH (basified 0.1% concentrated aqueous ammonium hydroxide solution) in dichloromethane to give the title compound as a racemate. The enantiomers were separated by normal-phase HPLC using a ChiralCel® OD column, eluting with 40% hexane in ethanol (0.1% diethylamine used as a modifier) to afford the title compound as the second enantiomer to elute. MS: m/z=319.2 (M+1).

Workup

  1. customThe catalyst was removed by filtration through Celite®
  2. washwashed thoroughly with methanol
  3. concentrationThe filtrate was concentrated
  4. customthe residue was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  5. washThe organic layer was washed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography on silica gel
  9. washeluting with dichloromethane initially

Sources & evidence

ORD record
ord-224dc2879f3e4a5f8318f715f9b919be
Source dataset
uspto-grants-2013_07
Patent number
US08481556B2

Reaction notes

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