Methanol → Methyl (2R,4S)-4-hydroxypyrrolidine-2-carboxylate hydrochloride

Temperature

22.5 °C

To a suspension of trans-4-hydroxy-D-proline hydrochloride (150 g, 0.89 mol, 1 equivalent) in methanol (1.25 L), thionyl chloride (130 mL, 1.79 mol, 2 equivalents) was added drop-wise at 0-5° C. Then the reaction mixture was stirred for 4 hours at 20-25° C. The reaction mixture was concentrated under reduced pressure. This crude material was stirred in a mixture of ethanol-methyl tert-butyl ether (1:4, 750 mL) for 30 minutes and the solid was collected by filtration. The wet cake was dried in a vacuum tray dryer for 8 hours at about 50° C. to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.03-2.23 (m, 2H), 3.06 (d, 1H, J=12.0 Hz), 3.37 (dd, 2H, J=4.5 Hz, J=12.0 Hz), 3.75 (s, 3H), 4.41-4.48 (m, 2H), 5.64 (bs, 1H), 9.43 (bs, 1H), 10.48 (bs, 1H).

1. additionwas added drop-wise at 0-5° C
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. stirringThis crude material was stirred in a mixture of ethanol-methyl tert-butyl ether (1:4, 750 mL) for 30 minutes
4. filtrationthe solid was collected by filtration
5. customThe wet cake was dried in a vacuum tray dryer for 8 hours at about 50° C.

ORD record

ord-ffa1dcf215d34e1287ee19d4fb164e00

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08648074B2