Sodium borohydride → 4-(R)-[2-(S)-Amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

HRID 20348

Reaction equation

HRID 20348 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([OH:29])[C@@H:14]([N+:26]([O-])=O)[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22]C(=O)C)[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>CO.[Ni](Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([C@@H:13]([OH:29])[C@@H:14]([NH2:26])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)[CH2:11][O:10][C:9]1([CH3:31])[CH3:30])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 685609864-(R)-[3-(3-Acetoxyphenyl)-1-(R)-hydroxy-2-(S)-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Product 1

HCID 685597324-(R)-[2-(S)-Amino-1-(S)-hydroxy-3-(3-hydroxyphenyl)-propyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

Add nickel (II) chloride (6.0 g, 46.1 mmol) to a solution of 4-(R)-[3-(3-acetoxyphenyl)-1-(R)-hydroxy-2-(S)-nitropropyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (18.37 g, 41.9 mmol) in dry methanol (900 mL). Cool in an ice bath and portionwise sodium borohydride (6.34 g, 167.6 mmol) over 8 minutes. Stir for 10 minutes. And concentrate. Partition the residue between ethyl acetate (200 mL) and water (200 mL), filter through Celite® and wash with ethyl acetate. Wash the organic layer with saturated aqueous sodium chloride, combine aqueous washes and extract with ethyl acetate. Combine the organic layers, dry (magnesium sulfate), filter and concentrate to give the desired compound as a crude foam. Suspend the Celite® cake in ethyl acetate, filter, wash with saturated aqueous sodium chloride, dry (magnesium sulfate), filter and concentrate to obtain more desired compound.

Workup

  1. temperatureCool in an ice bath
  2. concentrationAnd concentrate
  3. customPartition the residue between ethyl acetate (200 mL) and water (200 mL)
  4. filtrationfilter through Celite®
  5. washwash with ethyl acetate
  6. washWash the organic layer with saturated aqueous sodium chloride
  7. extractionextract with ethyl acetate
  8. dry with materialdry (magnesium sulfate)
  9. filtrationfilter
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-a887d5da444d4d0aae8eef16fd369179
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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