1,3-Diisobutyryloxy-2-(2,4-difluorophenyl)-2-propanol → (R)-2-(2,4-difluorophenyl)-3-isobutyryloxy-1,2-propanediol

HRID 1003779Notes

Reaction equation

HRID 1003779 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([OH:24])([CH2:17][O:18]C(=O)C(C)C)[CH2:10][O:11][C:12](=[O:16])[CH:13]([CH3:15])[CH3:14]>C([O-])(=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:24])([CH2:10][O:11][C:12](=[O:16])[CH:13]([CH3:14])[CH3:15])[CH2:17][OH:18]

Participants

3

Reactant 1

HCID 112908691,3-Diisobutyryloxy-2-(2,4-difluorophenyl)-2-propanol

Product 1

HCID 11150004(R)-2-(2,4-difluorophenyl)-3-isobutyryloxy-1,2-propanediolYield 94.8%

Reagents, catalysts & solvents 1

HCID 175AcetateSolvent

Procedure

A 200 ml reaction vessel was charged with 2 g of 2-(2,4-difluorophenyl)-1,3-diisobutyryloxy-2-propanol, 100 mg of Lipase D made by Amano Pharmaceutical Co., Ltd. (derived from Rhizopus delemer, Enzyme No. 6), 90 ml of 50 mM acetate buffer (pH 5) and 10 ml of cyclohexame The resulting mixture was stirred at 30° C. to react for 18 hours. After the reaction liquid was extracted three times with 50 ml of ethyl acetate, the organic layers were combined and the combined organic layer was washed with saturated aqueous solution with sodium bicarbonate and with saturated aqueous solution with sodium chloride and further dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by means of column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/2) to give 1.51 g of oily (R)-2-(2,4-difluorophenyl)-3-isobutyryloxy-1,2-propanediol. An optical purity thereof was determined in the same manner as Example 35.

Workup

  1. customA 200 ml reaction vessel
  2. customto react for 18 hours
  3. customAfter the reaction liquid
  4. extractionwas extracted three times with 50 ml of ethyl acetate
  5. washthe combined organic layer was washed with saturated aqueous solution with sodium bicarbonate and with saturated aqueous solution with sodium chloride
  6. dry with materialfurther dried over anhydrous sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was purified by means of column chromatography on silica gel (eluent: n-hexane/ethyl acetate=3/2)

Sources & evidence

ORD record
ord-e4554d9a2bf942d3bde98683556aeb98
Source dataset
uspto-grants-2000_04
Patent number
US06046354

Reaction notes

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