Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)- → (2R,3S,5S)-5-benzyloxymethyl-2-(2,2-dimethylpropoxy)-3-methylmorpholine

HRID 20401

Reaction equation

HRID 20401 reaction equation
C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O.[CH2:16]([O:23][CH2:24][C@H:25]([NH:28][C@@H:29]([CH3:43])[CH:30]([O:37][CH2:38]C(C)(C)C)[O:31][CH2:32][C:33]([CH3:36])([CH3:35])[CH3:34])CO)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:16]([O:23][CH2:24][C@@H:25]1[NH:28][C@@H:29]([CH3:43])[C@@H:30]([O:31][CH2:32][C:33]([CH3:34])([CH3:35])[CH3:36])[O:37][CH2:38]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1.[CH2:16]([O:23][CH2:24][C@@H:25]1[NH:28][C@@H:29]([CH3:43])[C@H:30]([O:31][CH2:32][C:33]([CH3:34])([CH3:35])[CH3:36])[O:37][CH2:38]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 2

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-HCID 68563577(R)-3-benzyloxy-2-[(S)-2,2-bis-(2,2-dimethylpropoxy)-1-methylethylamino]-propan-1-ol

Product 2

HCID 68562611(2R,3S,5S)-5-benzyloxymethyl-2-(2,2-dimethylpropoxy)-3-methylmorpholineYield 40%HCID 68562665(2S,3S,5S)-5-benzyloxymethyl-2-(2,2-dimethylpropoxy)-3-methylmorpholineYield 39%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Add camphorsulfonic acid (1.69 g, 7.28 mmol) to (R)-3-benzyloxy-2-[(S)-2,2-bis-(2,2-dimethylpropoxy)-1-methylethylamino]-propan-1-ol (1.60 g, 4.04 mmol) in toluene (65 mL) and heat to 100° C. for 1 hour. Cool to room temperature, dilute with ethyl acetate, wash with 2 N sodium hydroxide and saturated aqueous sodium chloride. Dry (magnesium sulfate), filter and concentrate. Purify (silica gel chromatography using deactivated silica gel prepared as previously described, eluting with 10:90 to 70:30 ethyl acetate:hexanes) to give the desired compounds (2S,3S,5S)-5-benzyloxymethyl-2-(2,2-dimethylpropoxy)-3-methylmorpholine (490 mg, 39% top spot,) and (2R,3S,5S)-5-benzyloxymethyl-2-(2,2-dimethylpropoxy)-3-methylmorpholine (495 mg, 40% bottom spot).

Workup

  1. temperatureCool to room temperature
  2. washwash with 2 N sodium hydroxide and saturated aqueous sodium chloride
  3. dry with materialDry (magnesium sulfate)
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify (silica gel chromatography
  7. customprepared
  8. washeluting with 10:90 to 70:30 ethyl acetate

Sources & evidence

ORD record
ord-6f04a1bfd3da46f789e6895417b09b8b
Source dataset
uspto-grants-2010_06
Patent number
US07745438B2

Linked notes

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