General procedure for the synthesis of (2S,4S)-N-Cbz-4-hydroxypyrrolidine-2-carboxylic acid from (2S,4R)-Cbz-4-methanesulfonyloxyproline methyl ester: firstly, 708 g of water and 337 g of 48% sodium hydroxide solution were added to 928 g of the crude product obtained by reference to Example 3. The temperature of the mixture was raised to 80°C and the reaction was ripened at this temperature for 3 hours. Upon completion of the maturation, the temperature was kept constant and 146 g of solvent was distilled under reduced pressure until the pressure was reduced to 13 kPa. Subsequently, the mixture was cooled to 20°C, 180 g of 48% sodium hydroxide solution was added and aged at 25°C for 12 hours. The amount of cis-Benzyloxycarbonyl-4-hydroxy-L-proline in the reaction solution was determined by analysis to be 2.19 mol (81.0% yield based on trans-4-hydroxy-L-proline). Next, 35 g of toluene was added to the hydrolysis reaction solution and the mixture was concentrated under reduced pressure at 7 kPa and 40 °C to distill 332 g of solvent. Then, 161 g of concentrated sulfuric acid was added dropwise to the concentrated solution and the pH was adjusted to 1.3. After acidic adjustment, 710 g of tetrahydrofuran and 354 g of water were added for layered separation. To the separated water layer, 356 g of tetrahydrofuran was added and the separation was performed again. All the separated tetrahydrofuran layers were combined and concentrated at 40 °C under reduced pressure at 26 kPa, resulting in 896 g of concentrate containing 2.12 mol of cis-Benzyloxycarbonyl-4-hydroxy-L-proline (90.2% yield) with a cis/trans ratio of 98.3/1.7.
