(1R,2R)-(-)-1,2-Cyclohexanedicarboxylic acid

2305-32-0

46022-05-3

Methanol (500 mL) and isopropanol (500 mL) were added to a round-bottomed flask, followed by the addition of racemic trans-1,2-cyclohexanedicarboxylic acid (100 g). Under stirring, (R)-1-phenylethylamine (74 mL) was added slowly over 30 min and the reaction mixture was stirred continuously at 30-40 °C for 2-3 h. The reaction was carried out by filtration. Upon completion of the reaction, the resulting solid was collected by filtration, washed with a mixture of methanol and isopropanol (50 mL each), and subsequently dried under reduced pressure to afford the crude (R)-1-phenylethylamine salt of (1R,2R)-1,2-cyclohexanedicarboxylic acid. The crude salt was dissolved in a solvent mixture of methanol (500 mL) and isopropanol (500 mL) and stirred at 65-70 °C for 2-3 hours, then cooled to room temperature and filtered. The solid was washed with a mixture of methanol and isopropanol (50 mL each) and dried again under reduced pressure. The dried solid was dissolved in a solution of about 2 N hydrochloric acid and extracted twice with ethyl acetate (first 1000 mL, second 200 mL). The organic phases were combined and washed with saturated brine solution (100 mL). Subsequently, ethyl acetate was removed by distillation under reduced pressure at 50-55 °C and cyclohexane was added to the residue. The separated solid was filtered, washed with cyclohexane and dried under vacuum at 45-50 °C for 8-10 hours. Finally, 29.4 g of (1R,2R)-1,2-cyclohexanedicarboxylic acid was obtained.