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

Participants

Reaction Steps

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+).

Provenance & Evidence