(R)-2-methoxycyclohexanol → (S)-2-methoxycyclohexanol

Participants

Reaction Steps

A 500-ml four-mouth flask equipped with a thermometer, dropping funnel, condenser, and stirrer was charged with 47.8 g (0.13 mol) of diparatoluoyl-L-tartaric acid anhydride, 13.0 g (0.1 mol) of (RS)-2-methoxycyclohexanol, 1.2 g of anhydrous iron trichloride, and 300 ml of toluene. After heating under reflux for 10 hours, the reaction solution was analyzed by liquid chromatography. The result of analysis indicated the formation of diparatoluoyl-L-tartaric acid-mono(2-methoxy)cyclohexyl ester (92%). Time for peak detection was 35 minutes in the case of (R)-2-methoxycyclohexanol ester and 37 minutes in the case of (S)-2-methoxycyclohexanol ester. Diparatoluoyl-L-tartaric acid anhydride remaining unreacted was filtered off, and the filtrate was concentrated and subjected to column chromatography (using a column filled with silica gel “Kieselgel 60”, 60-230 mesh, made by Merck). Chromatographic separation was carried out by using a mixture of acetonitrile and cylohexane in varied ratios. There was obtained 9.5 g of diparatoluoyl-L-tartaric acid-mono(R)-2-methoxycyclohexyl ester in the first eluate. Analysis by liquid chromatography indicated that the ester is composed of (R)-form and (S)-form in a ratio of approximately 99/1. This compound was hydrolyzed by 30 ml in 1N aqueous solution of sodium hydroxide at 30° C. for 5 hours with stirring. The hydrolyzate was extracted three times with 100 ml of dichloroethane. The extract was concentrated to give 2.8 g of concentrated solution containing (R)-2-methoxycyclohexanol. The concentrated solution was distilled under reduced pressure (2.6 kPa) to give 2.2 g of distillate having an angle of rotation of −75° (c=2.10 in dichloromethane). The last eluate obtained by chromatographic separation was treated in the same manner as above to give 2.1 g of (S)-2-methoxycyclohexanol having an angle of rotation of +74° (c=2.00 in dichloromethane).

Provenance & Evidence