Sodium borohydride → (2R,3S,5R)-5-[(1S,2S)-2-Amino-3-(2-ethylphenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl ester

HRID 20432Notes

Reaction equation

HRID 20432 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:13]([C@@H:14]([OH:28])[C@@H:15]([N+:25]([O-])=O)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][CH3:24])[CH2:12][O:11][C@@H:10]([O:29][CH2:30][C:31]([CH3:34])([CH3:33])[CH3:32])[C@@H:9]1[CH3:35])=[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:13]([C@@H:14]([OH:28])[C@@H:15]([NH2:25])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[CH2:23][CH3:24])[CH2:12][O:11][C@@H:10]([O:29][CH2:30][C:31]([CH3:32])([CH3:34])[CH3:33])[C@@H:9]1[CH3:35])=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 68563437HCID 68563437, compound

Product 1

HCID 68560674(2R,3S,5R)-5-[(1S,2S)-2-Amino-3-(2-ethylphenyl)-1-hydroxypropyl]-2-(2,2-dimethylpropoxy)-3-methylmorpholine-4-carboxylic acid tert-butyl esterYield 85%

Reagents, catalysts & solvents 2

HCID 24385Nickel DichlorideCatalystHCID 887MethanolSolvent

Procedure

Dissolve the mixture of diastereomers from the previous reaction containing (2R,3S,5R)-2-(2,2-dimethylpropoxy)-5-[(1R,2S)-3-(2-ethylphenyl)-1-hydroxy-2-nitropropyl]-3-methylmorpholine-4-carboxylic acid tert-butyl ester in dry methanol (12 mL) and add nickel (II) chloride (267 mg, 2.06 mmol). To the resulting suspension, add sodium borohydride (284 mg, 7.5 mmol) portion-wise over 1 minute. After 30 minutes, quench with water and reduce the volume on the rotary evaporator. Add more water and saturated aqueous sodium chloride. Extract with ethyl acetate. Combine the extracts, dry (sodium sulfate), filter and concentrate to give a diastereomeric mixture of amines containing the desired compound as a light brown oil (418 mg, 85%).

Workup

  1. dissolutionDissolve
  2. additionthe mixture of diastereomers
  3. customfrom the previous reaction
  4. customquench with water
  5. customon the rotary evaporator
  6. additionAdd more water and saturated aqueous sodium chloride
  7. extractionExtract with ethyl acetate
  8. dry with materialdry (sodium sulfate)
  9. filtrationfilter
  10. concentrationconcentrate
  11. customto give

Sources & evidence

ORD record
ord-cf1cd535a69742338a579dc59fe0dd33
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

Loading…