Sodium borohydride → cis-6-(3,5-Difluorophenyl)-4-hydroxy-3,3-dimethylpiperidin-2-one

HRID 1866655Notes

Reaction equation

HRID 1866655 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[NH:14][C:13](=[O:15])[C:12]([CH3:17])([CH3:16])[C:11](=[O:18])[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.[BH4-].[Na+]>C1COCC1.CO>[F:8][C:6]1[CH:5]=[C:4]([C@H:9]2[NH:14][C:13](=[O:15])[C:12]([CH3:16])([CH3:17])[C@@H:11]([OH:18])[CH2:10]2)[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 669735216-(3,5-Difluorophenyl)-3,3-dimethylpiperidine-2,4-dione

Product 1

HCID 66973592cis-6-(3,5-Difluorophenyl)-4-hydroxy-3,3-dimethylpiperidin-2-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-(3,5-difluorophenyl)-3,3-dimethylpiperidine-2,4-dione from Step A (20.18 g, 80 mmol) in THF (600 mL) and CH3OH (25 mL) at 0° C. was added NaBH4 (4.57 g, 121 mmol). After 2.5 h, the reaction mixture was quenched with H2O (200 mL) and concentrated in vacuo. The residue was partitioned between H2O (600 mL), saturated aqueous NaHCO3 (200 mL) and EtOAc (1 L). The organic layer was separated and the aqueous layer was extracted with EtOAc (600 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel chromatography, eluting with a gradient of CH2Cl2:CH3OH—100:0 to 88:12, to give the title compound, which contained approximately 20% of the corresponding trans-isomer. MS: m/z=256 (M+1).

Workup

  1. customthe reaction mixture was quenched with H2O (200 mL)
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between H2O (600 mL), saturated aqueous NaHCO3 (200 mL) and EtOAc (1 L)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (600 mL)
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with a gradient of CH2Cl2

Sources & evidence

ORD record
ord-70acd1bb63d44a129fbbf08fea7df658
Source dataset
uspto-grants-2009_12
Patent number
US07629338B2

Reaction notes

Loading…