{(1R,2R)-2-benzyloxy-1-[2-(4-chlorophenyl)-2-oxoethoxymethyl]propyl}carbamic acid t-butyl ester → (3R,5R)-3-((R)-1-benzyloxyethyl)-5-(4-chlorophenyl)morpholine

HRID 16376Notes

Reaction equation

HRID 16376 reaction equation
C(OC(=O)[NH:7][C@H:8]([CH2:19][O:20][CH2:21][C:22]([C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=1)=O)[C@H:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH3:10])(C)(C)C>Cl.C(OCC)(=O)C>[CH2:12]([O:11][C@@H:9]([C@H:8]1[CH2:19][O:20][CH2:21][C@@H:22]([C:24]2[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=2)[NH:7]1)[CH3:10])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

3

Reactant 1

HCID 67373088{(1R,2R)-2-benzyloxy-1-[2-(4-chlorophenyl)-2-oxoethoxymethyl]propyl}carbamic acid t-butyl ester

Product 1

HCID 67372082(3R,5R)-3-((R)-1-benzyloxyethyl)-5-(4-chlorophenyl)morpholineYield 74.2%

Reagents, catalysts & solvents 1

HCID 21866389Hydrogen chloride-ethyl acetateSolvent

Procedure

A solution of {(1R,2R)-2-benzyloxy-1-[2-(4-chlorophenyl)-2-oxoethoxymethyl]propyl}carbamic acid t-butyl ester (2.61 g) in a 4 N hydrochloric acid/ethyl acetate solution (40 mL) was stirred at room temperature for 1 hour. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with methanol (30 ml). While cooling with ice, to the stirring solution was added sodium cyanoborohydride (733 mg), and the resultant solution was stirred overnight at room temperature. Solvent was removed by distillation under reduced pressure. The resultant product was diluted with ethyl acetate. This solution was successively washed with saturated sodium bicarbonate water and brine, and the organic layer was then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 95/5→3/2), to thereby obtain the titled compound (1.435 g). The physical properties of this crude product were as follows.

Workup

  1. customSolvent was removed by distillation under reduced pressure
  2. additionthe resultant product was diluted with methanol (30 ml)
  3. temperatureWhile cooling with ice, to the stirring solution
  4. additionwas added sodium cyanoborohydride (733 mg)
  5. customSolvent was removed by distillation under reduced pressure
  6. additionThe resultant product was diluted with ethyl acetate
  7. washThis solution was successively washed with saturated sodium bicarbonate water and brine
  8. dry with materialthe organic layer was then dried over anhydrous magnesium sulfate
  9. customSolvent was removed by distillation under reduced pressure
  10. customthe resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 95/5→3/2)

Sources & evidence

ORD record
ord-4d46a0e7bebb446ebd59cd1aab9ef109
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Reaction notes

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