1,2,5-Menthyl-5(S)-acetoxy-[1,3]-oxathiolene-2-(R)-carboxylate

108-24-7

147126-62-3

147126-65-6

147027-09-6

(1R,2S,5R)-5-methyl-2-isopropylcyclohexyl-5R-hydroxy-1,3-oxathiolane-2R-carboxylate (300 g, 1.04 mol) was suspended in diisopropyl ether (1050 ml) at 0-5 °C, pyridine (103.5 g, 1.31 mol) and 4-dimethylaminopyridine (0.35 g, 3 mmol ) and stirred under nitrogen protection. Acetic anhydride (123.6 g, 1.21 mol) was diluted with diisopropyl ether (380 ml) and added dropwise to the reaction mixture at 0-8 °C over about 2 hours. The reaction was continued to be stirred at 3-8 °C for 10 h to ensure complete reaction (monitored by TLC). Upon completion of the reaction, the mixture was warmed to room temperature (20-30 °C) and diluted with diisopropyl ether. Subsequently, it was washed sequentially with 5% v/v aqueous acetic acid (2 x 400 ml) and warm water (2 x 500 ml, ca. 40 °C) to completely remove the pyridine. The organic layer was concentrated under reduced pressure at less than 45 °C to give a solid residue. Hexane (390 ml) was added to the residue, heated to about 50 °C and held for 15-20 minutes, then cooled to room temperature and stirred for 30 minutes. The product slurry was further cooled to -6°C to -10°C and stirred at that temperature for 3 hours. The product was collected by filtration and washed with pre-cooled hexane (150 ml, -6°C to -8°C). The product was dried under reduced pressure at about 45 °C for 6 h to give (2R,5S)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl-5-acetoxy-1,3-oxathiolane-2-carboxylate in a yield of 279.6 g and HPLC purity (RI detector) of 99.87%. The product was a mixture of (2R,5R) and (2R,5S) isomers with (2R,5R) as the major component (≥90%) and (2R,5S) as the minor component (≤10%) as determined by HPLC (RI detector) analysis. The ratio of isomers of the acetoxy compounds had no significant effect on the ratio of α:β isomers formed in the glycosidization reaction.