Potassium Carbonate → tert-butyl[(3S,5S)-5-(2-fluorophenyl)-2-oxopiperidin-3-yl]carbamate

HRID 406543Notes

Reaction equation

HRID 406543 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([C:21]([O:23]C)=O)[CH2:10][CH:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[F:20])[C:12]#[N:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H].C(=O)([O-])[O-].[K+].[K+]>C(O)C.[Ni]>[F:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C@H:11]1[CH2:12][NH:13][C:21](=[O:23])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 68748587Methyl N-(tert-butoxycarbonyl)-4-(2-fluorophenyl)-5-nitrilonorvalinateHCID 178418361HCID 178418361, compound

Product 1

HCID 86665197tert-butyl[(3S,5S)-5-(2-fluorophenyl)-2-oxopiperidin-3-yl]carbamate

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 702EthanolSolvent2×

Conditions

Temperature
23 °C

Procedure

To a solution of methyl N-(tert-butoxycarbonyl)-4-(2-fluorophenyl)-5-nitrilonorvalinate (3.88 g, 11.5 mmol) in ethanol (50 mL) was added Raney nickel (slurry in water, ca. 10 g). The mixture was placed under a balloon of hydrogen and the reaction was stirred at 23° C. for 4 h. The mixture was filtered and concentrated to afford a mixture of 4 diastereoisomers. A solution of this residue in ethanol (100 mL) was stirred in the presence of solid potassium carbonate (1.30 g, 9.44 mmol) at 60° C. for 2 h. The bulk of the ethanol was removed under reduced pressure and the remaining slurry was diluted with water to afford a white precipitate. The precipitate was filtered, washed with water and then dried under vacuum at 40° C. for 18 h. The enantiomers were separated using normal-phase HPLC using a ChiralPak® AD column, eluting with 40% hexane in ethanol (0.1% diethylamine used as a modifier) to afford the title compound as the second major enantiomer to elute. MS: m/z=331.1 (M+Na).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationconcentrated
  3. customto afford
  4. additiona mixture of 4 diastereoisomers
  5. customThe bulk of the ethanol was removed under reduced pressure
  6. additionthe remaining slurry was diluted with water
  7. customto afford a white precipitate
  8. filtrationThe precipitate was filtered
  9. washwashed with water
  10. customdried under vacuum at 40° C. for 18 h
  11. customThe enantiomers were separated
  12. washeluting with 40% hexane in ethanol (0.1% diethylamine

Sources & evidence

ORD record
ord-757099e6d6ab414d96aa37020d630626
Source dataset
uspto-grants-2014_06
Patent number
US08754096B2

Reaction notes

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