(2R,5R)-5-Hydroxy-1,3-oxathiolane-2-carboxylic acid (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester

40018-26-6

111969-64-3

147126-62-3

L-menthyl ethanedioate monohydrate (1.0 g, 4.34 mmol) and 1,4-dithiane-2,5-diol (396 mg, 2.60 mmol) were used as raw materials, dissolved in acetone (10 mL) and a catalytic amount of acetic acid (0.5 mL) was added. The mixed solution was pumped into a flow reactor at a total flow rate of 0.1 mL/min (where the flow rate of the L-menthylglycolate solution was 0.05 mL/min), and the reaction conditions were set to 125°C and 10 bar back pressure. Upon completion of the reaction, the progress of the reaction was monitored by thin layer chromatography (TLC) and gas chromatography (GC). Subsequently, the solvent was evaporated, the reaction mixture was cooled to 0°C-5°C, a 1% solution of triethylamine in heptane or hexane was added slowly dropwise and stirred at 0°C for 2-3 h to promote precipitate formation. The solid product was collected by filtration and washed with hexane to afford (2R,5R)-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyl)5-hydroxy-1,3-oxathiolane-2-carboxylate (1.1 g, 88% yield) as a white solid. The structure of the product was confirmed by 1H-NMR (400 MHz, CDCl3): δ 5.96 (s, 1H), 5.57 (d, 1H), 4.74 (s, 1H), 3.32-3.29 (m, 1H), 3.17-3.08 (dd, 1H), 2.02 (d, 2H), 1.70 (d, 1H), 1.51- 1.42 (m, 2H), 1.09-1.00 (m, 2H), 0.91 (d, 6H), 0.78 (d, 3H); 13C-NMR (100 MHz, CDCl3): δ 16.27, 20.69, 23.30, 26.16, 31.42, 34.11, 38.46, 40.35, 46.86, 46.07, 80.20, 101.22, 103.20, 172.18; FT-IR (Neat): 3456, 2956, 2864, 1731, 1457, 1387, 1288, 1196, 1041, 986 cm-1. Reaction conditions: flow rate of 0.1 mL/min, retention time 20 min, reaction temperature 50°C to 125°C, and crystallization conditions of 1% triethylamine in heptane/hexane solution.