{(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 1677063Notes

Reaction equation

HRID 1677063 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 4 N hydrochloric acid/ethyl acetate solution (40 mL) of {(1R,2R)-2-benzyloxy-1-[2-(4-chlorophenyl)-2-oxoethoxymethyl]propyl}carbamic acid t-butyl ester (2.61 g) was stirred for 1 hour at room temperature. The solvent was removed under a vacuum, and methanol (30 mL) was added. Under ice-cooling, sodium cyanoborohydride (733 mg) was added, and the resultant was stirred overnight at room temperature. The solvent was removed under a vacuum, and the resultant was diluted with ethyl acetate and washed with saturated sodium bicarbonate aqueous solution and brine in sequence, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was removed under a vacuum, and the residue was purified with silica gel column chromatography (heptane/ethyl acetate 95/5→3/2), and the title compound (1.435 g) was obtained. The physical property values are as follows.

Workup

  1. customThe solvent was removed under a vacuum, and methanol (30 mL)
  2. additionwas added
  3. temperatureUnder ice-cooling
  4. additionsodium cyanoborohydride (733 mg) was added
  5. customThe solvent was removed under a vacuum
  6. additionthe resultant was diluted with ethyl acetate
  7. washwashed with saturated sodium bicarbonate aqueous solution and brine in sequence
  8. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  9. customThe solvent was removed under a vacuum
  10. customthe residue was purified with silica gel column chromatography (heptane/ethyl acetate 95/5→3/2)

Sources & evidence

ORD record
ord-6fd82429df7040ae88af12b8f880cbac
Source dataset
uspto-grants-2011_08
Patent number
US08008293B2

Reaction notes

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