Dimethylformamide → 1-Benzyloxycarbonylamino-3-methoxy-2-propanol

HRID 2275802Notes

Reaction equation

HRID 2275802 reaction equation
[NH2:1][CH2:2][CH:3]([OH:7])[CH2:4][O:5][CH3:6].[C:8](Cl)(=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(N(CC)C(C)C)(C)C.CN(C=O)C>C1COCC1.CN(C)C1C=CN=CC=1>[OH:7][CH:3]([CH2:4][O:5][CH3:6])[CH2:2][NH:1][C:8](=[O:17])[O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10387Benzyl chloroformate2×HCID 81531DiisopropylethylamineHCID 1245101-Amino-3-methoxypropan-2-ol

Product 1

HCID 190124911-Benzyloxycarbonylamino-3-methoxy-2-propanol

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

5.0 g (47.6 mmol) of rac-1-amino-3-methoxypropan-2-ol were initially charged in THF (158 ml), and 7.36 ml (52.3 mmol) of benzyl chlorocarbonate, 24.85 ml (142.7 mmol) of N,N-diisopropyl ethyl amine and 1.16 g (9.5 mmol) of 4-dimethylaminopyridine were added. The reaction mixture was stirred at RT for 16 h. 3.7 ml (26.2 mmol) of benzyl chlorocarbonate and then 15 ml of DMF were added, and the reaction solution was stirred at RT overnight. The mixture was concentrated and diluted with ethyl acetate. The mixture was then washed with water, saturated aqueous sodium bicarbonate solution and with saturated aqueous sodium chloride solution. The organic phase was dried over sodium sulphate, filtered off and concentrated. The aqueous phase was concentrated, the residue was taken up in ethyl acetate, the mixture was washed with saturated aqueous sodium bicarbonate solution and with saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered off and concentrated. Both fractions were combined and purified by silica gel chromatography (dichloromethane/methanol gradient: from 100:0 to 10:1). This gave 12.16 g (81% of theory, purity 76%) of the target compound.

Workup

  1. stirringthe reaction solution was stirred at RT overnight
  2. concentrationThe mixture was concentrated
  3. additiondiluted with ethyl acetate
  4. washThe mixture was then washed with water, saturated aqueous sodium bicarbonate solution and with saturated aqueous sodium chloride solution
  5. dry with materialThe organic phase was dried over sodium sulphate
  6. filtrationfiltered off
  7. concentrationconcentrated
  8. concentrationThe aqueous phase was concentrated
  9. washthe mixture was washed with saturated aqueous sodium bicarbonate solution and with saturated aqueous sodium chloride solution
  10. dry with materialdried over sodium sulphate
  11. filtrationfiltered off
  12. concentrationconcentrated
  13. custompurified by silica gel chromatography (dichloromethane/methanol gradient: from 100:0 to 10:1)

Sources & evidence

ORD record
ord-0603edb8eb4f47798bcec91033ab3dbb
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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