Benzyl chloroformate → (3R,5R)-3-((R)-1-hydroxyethyl)-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester

HRID 16388

Reaction equation

HRID 16388 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[NH:15][C@@H:14]([C@H:16]([OH:18])[CH3:17])[CH2:13][O:12][CH2:11]2)[CH:5]=[C:6]([F:9])[C:7]=1[F:8].O.C(=O)(O)[O-].[Na+].Cl[C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27]>O1CCCC1.O.C(OCC)(=O)C>[CH2:29]([O:28][C:26]([N:15]1[C@H:10]([C:4]2[CH:3]=[C:2]([F:1])[C:7]([F:8])=[C:6]([F:9])[CH:5]=2)[CH2:11][O:12][CH2:13][C@@H:14]1[C@H:16]([OH:18])[CH3:17])=[O:27])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 3

HCID 10387Benzyl chloroformate2×HCID 67374002(R)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholin-3-yl]ethanolHCID 86585896Sodium bicarbonate water

Product 1

HCID 67373415(3R,5R)-3-((R)-1-hydroxyethyl)-5-(3,4,5-trifluorophenyl)morpholine-4-carboxylic acid benzyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (R)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethanol (2 g) in tetrahydrofuran (20 mL) was added saturated sodium bicarbonate water (20 mL) and benzyl chloroformate (1.31 mL). After stirring the reaction solution at room temperature for 16 hours, benzyl chloroformate (1.33 mL) was further added thereto, and the mixture was then stirred for another 20 hours. The resultant solution was diluted with water and ethyl acetate. The organic layer was partitioned, washed with brine, and 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), to thereby obtain the titled compound (880 mg). The physical properties of this crude product were as follows.

Workup

  1. stirringthe mixture was then stirred for another 20 hours
  2. customThe organic layer was partitioned
  3. washwashed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customSolvent was removed by distillation under reduced pressure
  6. customthe resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate)

Sources & evidence

ORD record
ord-a67cc7744e6c493b8540664ed49f314e
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Linked notes

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