Sodium borohydride → (2R,3S,5R)-5-[2-Amino-3-(3-benzyloxy-5-fluoro-phenyl)-1-hydroxy-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl ester

HRID 20443Notes

Reaction equation

HRID 20443 reaction equation
[BH4-].[Na+].[C:3]([O:7][C:8]([N:10]1[C@@H:15]([C@@H:16]([OH:37])[C@@H:17]([N+:34]([O-])=O)[CH2:18][C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH:20]=2)[CH2:14][O:13][C@@H:12]([O:38][CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C@@H:11]1[CH3:44])=[O:9])([CH3:6])([CH3:5])[CH3:4]>CO.[Ni](Cl)Cl>[C:3]([O:7][C:8]([N:10]1[C@@H:15]([CH:16]([OH:37])[CH:17]([NH2:34])[CH2:18][C:19]2[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([O:26][CH2:27][C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH:20]=2)[CH2:14][O:13][C@@H:12]([O:38][CH2:39][C:40]([CH3:43])([CH3:42])[CH3:41])[C@@H:11]1[CH3:44])=[O:9])([CH3:4])([CH3:6])[CH3:5]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 68561860HCID 68561860, compound

Product 1

HCID 68561913(2R,3S,5R)-5-[2-Amino-3-(3-benzyloxy-5-fluoro-phenyl)-1-hydroxy-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl esterYield 77.3%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

Add sodium borohydride (1.66 g, 43.87 mmol) to (2R,3S,5R)-5-[(1R,2S)-3-(3-benzyloxy-5-fluoro-phenyl)-1-hydroxy-2-nitro-propyl]-2-(2,2-dimethyl-propoxy)-3-methyl-morpholine-4-carboxylic acid tert-butyl ester (5.89 g, 9.97 mmol) and nickel chloride (2.07 g, 15.95 mmol) in methanol (100 mL) at room temperature and stir 30 minutes. Add water (˜10 mL) and concentrate. Dilute with ethyl acetate and filter through celite. Partition between ethyl acetate and saturated aqueous sodium chloride. Wash the organic layer with saturated aqueous sodium chloride, dry (sodium sulfate), filter and concentrate to give 4.32 g (77.3%) of the desired compound as a white solid.

Workup

  1. concentrationAdd water (˜10 mL) and concentrate
  2. additionDilute with ethyl acetate
  3. filtrationfilter through celite
  4. customPartition between ethyl acetate and saturated aqueous sodium chloride
  5. washWash the organic layer with saturated aqueous sodium chloride
  6. dry with materialdry (sodium sulfate)
  7. filtrationfilter
  8. concentrationconcentrate

Sources & evidence

ORD record
ord-b35f4bfc39344c96bc50d6cdb231fab3
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

Loading…