104706-47-0

51-35-4

104706-47-0

Example 1: Preparation of (R)-3-hydroxypyrrolidine hydrochloride (Formula VII): cyclohexanol (80 liters) was added to the reactor and heated to 155°C. Water was removed by azeotropic distillation until the water content in the solvent did not exceed 0.2% (w/w). The solvent was then cooled to 45 °C and (2S,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid (15 kg) was added and stirred for 10 min. Methyl isobutyl ketone (4.275 liters) was added to the reaction mixture, reheated to 154°C and maintained at this temperature for 5 hours of reaction. The reaction process was monitored by thin layer chromatography. Upon completion of the reaction, the reaction mixture was cooled to 0 °C under nitrogen protection and the pH was adjusted to 1.0-2.0 with ether-HCl (41 l). pH adjustment was completed, the temperature was raised to 25 °C and maintained for 2-3 h. The reaction mixture was then heated to 154 °C and maintained at this temperature for 5 h. The solid product was filtered and the reaction mixture was then heated to 154 °C. The solid product was collected by filtration and washed successively with ethyl acetate (30 liters in two portions) and isopropanol (15 liters). The wet solid was dried by suction for 1-2 hours and then dried under reduced pressure at 55°C for 5 hours to give 10.7 kg (R)-3-hydroxypyrrolidine hydrochloride in 76% yield and 98.5% HPLC purity.