cis-3-[2-(4-Fluorophenyl)-5-methyloxazol-4-ylmethoxy]cyclohexanol → (1r,3s)-3-[2-(4-Fluorophenyl)-5-methyloxazol4-ylmethoxy]cyclohexanol

HRID 858192Notes

Reaction equation

HRID 858192 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:22])=[C:11]([CH2:13][O:14][C@@H:15]3[CH2:20][CH2:19][CH2:18][C@H:17]([OH:21])[CH2:16]3)[N:12]=2)=[CH:4][CH:3]=1>C(OC=C)(=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]([CH3:22])=[C:11]([CH2:13][O:14][C@H:15]3[CH2:20][CH2:19][CH2:18][C@@H:17]([OH:21])[CH2:16]3)[N:12]=2)=[CH:6][CH:7]=1

Participants

3

Reactant 1

HCID 59094684cis-3-[2-(4-Fluorophenyl)-5-methyloxazol-4-ylmethoxy]cyclohexanol

Product 1

HCID 59094686(1r,3s)-3-[2-(4-Fluorophenyl)-5-methyloxazol4-ylmethoxy]cyclohexanol

Reagents, catalysts & solvents 1

HCID 7904Vinyl AcetateSolvent

Procedure

25 g of rac-cis-3-[2-(4-fluorophenyl)-5-methyloxazol-4-ylmethoxy]cyclohexanol are dissolved in 320 ml of vinyl acetate, and 1.3 g of Chirazyme L-2 Lyo (Boehringer Mannheim) are added. The mixture is stirred at room temperature for three hours (checked by LC-MS for 40–45% conversion) and the enzyme is then filtered off and washed with ethyl acetate, and the solvent is removed under reduced pressure. The residue is purified by flash chromatography on silica gel (n-heptane/ethyl acetate=3:1). This gives 8 g of (1 R, 3S)-3-[2-(4-fluorophenyl)-5-methyloxazyol-4-ylmethoxy]cyclohexyl acetate as a colorless oil. C19H22FNO4 (347.39), MS (ESI): 348 (M+H+). The acetate is taken up in 170 ml of methanol and, after addition of 27 ml of 2N aqueous sodium hydroxide solution, stirred at room temperature for one hour. Most of the solvent is removed under reduced pressure. After addition of in each case 150 ml of water and ethyl acetate, the organic phase is washed with sodium chloride solution. The organic phase is dried over magnesium sulfate and the solvent is removed under reduced pressure. This gives 6.7 g of 3-(1R,3S)-3-[2-(4-fluorophenyl)-5-methyloxazol4-ylmethoxy]cyclohexanol as a yellowish solid. C17H20FNO3 (305.35), MS (ESI): 306 (M+H+).

Workup

  1. addition1.3 g of Chirazyme L-2 Lyo (Boehringer Mannheim) are added
  2. filtrationthe enzyme is then filtered off
  3. washwashed with ethyl acetate
  4. customthe solvent is removed under reduced pressure
  5. customThe residue is purified by flash chromatography on silica gel (n-heptane/ethyl acetate=3:1)
  6. additionafter addition of 27 ml of 2N aqueous sodium hydroxide solution
  7. stirringstirred at room temperature for one hour
  8. customMost of the solvent is removed under reduced pressure
  9. additionAfter addition of in each case 150 ml of water and ethyl acetate
  10. washthe organic phase is washed with sodium chloride solution
  11. dry with materialThe organic phase is dried over magnesium sulfate
  12. customthe solvent is removed under reduced pressure

Sources & evidence

ORD record
ord-80bf0750d3114af88c045076ac65fb71
Source dataset
uspto-grants-2006_12
Patent number
US07148246B2

Reaction notes

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