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

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).

1. temperaturethe suspension was cooled to 5°-10° C
2. customunder 20° C
3. additionAfter completion of the dropwise addition
4. temperaturethe reaction mixture was warmed to 60°-62° C.
5. temperatureThe reaction mixture was then cooled to 25°-30° C. for crystallization
6. additionAfter completion of the dropwise addition
7. temperaturethe mixture was cooled to 0°-5° C.
8. stirringstirred for 1 hour
9. filtrationThe resulting crystal was collected by filtration
10. washwashed with diisopropyl ether (200 ml) twice
11. customThe washed crystal was dried in vacuo overnight

ORD record

ord-e0f6899a7f394d348f448e1c40b181ec

Source dataset

uspto-grants-1996_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05543525