Acetic Acid → (R)-3-benzyloxy-2-[(S)-2,2-bis-(2,2-dimethylpropoxy)-1-methylethylamino]-propan-1-ol

HRID 20404Notes

Reaction equation

HRID 20404 reaction equation
S([O-])([O-])(=O)=O.[Mg+2].[NH2:7][C@@H:8]([CH2:11][O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:9][OH:10].[CH3:20][C:21]([CH3:35])([CH3:34])[CH2:22][O:23][CH:24]([O:28][CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:25](=O)[CH3:26].C([BH3-])#N.[Na+].C(O)(=O)C>O1CCCC1>[CH2:13]([O:12][CH2:11][C@H:8]([NH:7][C@@H:25]([CH3:26])[CH:24]([O:23][CH2:22][C:21]([CH3:35])([CH3:34])[CH3:20])[O:28][CH2:29][C:30]([CH3:33])([CH3:31])[CH3:32])[CH2:9][OH:10])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 24083Sulfuric acid magnesium salt (1:1)HCID 5003444Sodium cyanoborohydrideHCID 141184082-Amino-3-(benzyloxy)propan-1-olHCID 862366811,1-Bis-(2,2-dimethylpropoxy)-propan-2-one

Product 1

HCID 68563577(R)-3-benzyloxy-2-[(S)-2,2-bis-(2,2-dimethylpropoxy)-1-methylethylamino]-propan-1-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add magnesium sulfate (30.23 g, 251.10 mmol) to (R)-2-amino-3-benzyloxypropan-1-ol (12.30 g, 67.87 mmol) and 1,1-bis-(2,2-dimethylpropoxy)-propan-2-one (23.45 g, 101.80 mmol) in tetrahydrofuran (100 mL) at room temperature and stir for 2 hours. Filter and concentrate. Dissolve in methanol (200 mL) and cool in an ice water bath. Add sodium cyanoborohydride (8.53 g, 135.73 mmol) and then acetic acid (4.08 g, 67.87 mmol) dropwise. Warm to room temperature, stir 2 hours and concentrate to −50 mL. Dilute with ethyl acetate (˜200 mL) and add water (˜50 ml) followed by 1 N sodium hydroxide (˜200 mL). Stir 20 minutes and dilute with saturated aqueous sodium chloride. Dry (sodium sulfate), filter and concentrate to give the title compounds.

Workup

  1. filtrationFilter
  2. concentrationconcentrate
  3. dissolutionDissolve in methanol (200 mL)
  4. temperaturecool in an ice water bath
  5. stirringstir 2 hours
  6. concentrationconcentrate to −50 mL
  7. additionDilute with ethyl acetate (˜200 mL)
  8. additionadd water (˜50 ml)
  9. stirringStir 20 minutes
  10. additiondilute with saturated aqueous sodium chloride
  11. dry with materialDry (sodium sulfate)
  12. filtrationfilter
  13. concentrationconcentrate

Sources & evidence

ORD record
ord-c901e896053a459a99d01ba379d2b102
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Reaction notes

Loading…