L-Hydroxyproline → 4-Hydroxy-L-proline methyl ester hydrochloride

Participants

Reaction Steps

In an atmosphere of nitrogen, (2S,4R)-2-carboxy-4-hydroxypyrrolidine (100 g, 0.763 mol) was suspended in methanol (400 ml) and the suspension was cooled to 5°-10° C. Then, thionyl chloride (99.8 g, 0.839 mol) was added dropwise thereto under 20° C. After completion of the dropwise addition, the reaction mixture was warmed to 60°-62° C. and stirred at this temperature for 1 hour. The reaction mixture was then cooled to 25°-30° C. for crystallization. To the mixture was added diisopropyl ether (180 ml) dropwise. After completion of the dropwise addition, the mixture was cooled to 0°-5° C. and stirred for 1 hour. The resulting crystal was collected by filtration and washed with diisopropyl ether (200 ml) twice. The washed crystal was dried in vacuo overnight to provide (2S,4R)-2-methoxycarbonyl-4-hydroxypyrrolidine hydrochloride (134.8 g).

Provenance & Evidence