Methanol → 1-Benzyl-3,4-dihydroxypyrrolidine-2,5-dione

Temperature

135 °C

A mixture of xylene, (1.2 L), benzylamine (120 g, 1.10 mol, 1.0 eq) and L-(+)-tartaric acid (173 g, 1.15 mol, 1.05 eq) were heated at 135° C. for 12 hr (flask jacket temperature). Upon reaction completion, the mixture was cooled to 65° C. and MeOH (120 mL, 1 vol) was added. The resulting mixture was stirred for 1 hr and the resulting suspension was cooled to 20° C. followed by the addition of EtOAc (480 mL). Stirring was continued at 10° C. for 2 hr. The crude product was isolated by filtration and washed with EtOAc (120 mL) and dried on the filter. The crude product was then taken up in MeOH (480 mL) and heated at a gentle reflux for 1 hr, then cooled to 20° C. and granulated for 1 hr. The suspension was filtered and the precipitate washed with MeOH (240 mL) and dried to give the title compound (191 g, 864 mmol, 79%) as a white granular solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.38-7.30 (m, 2H) 7.30-7.22 (m, 3 H) 6.32 (br. s., 1 H) 4.59 (d, J=14.8 Hz, 1 H) 4.53 (d, J=14.8 Hz, 1 H) 4.40 (br. D., J=4.3 Hz, 2 H). m/z (EI+) for C11H11NO4 221.0 (M)+.

1. customUpon reaction completion
2. temperaturethe mixture was cooled to 65° C.
3. temperaturethe resulting suspension was cooled to 20° C.
4. stirringStirring
5. waitwas continued at 10° C. for 2 hr
6. customThe crude product was isolated by filtration
7. washwashed with EtOAc (120 mL)
8. customdried on the filter
9. temperatureheated at
10. temperaturea gentle reflux for 1 hr
11. temperaturecooled to 20° C.
12. waitgranulated for 1 hr
13. filtrationThe suspension was filtered
14. washthe precipitate washed with MeOH (240 mL)
15. customdried

ORD record

ord-87a52c3998974f8998f04433070660d2

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09290496B2