Hydrochloric Acid → HCID 131734543, compound

Into a 200 mL four-mouthed flask were added benzyl 3-(2-methoxyacetyl)-2-oxopyrrolidine-1-carboxylate potassium salt (6.60 g) [mw. 329.39, 20.0 mmol], 1 mol/L aqueous hydrochloric acid solution (33 mL) and toluene (60 mL), and the mixture was stirred at room temperature for 30 min. After partitioning, the organic layer was washed with water (33 mL), and dried over magnesium sulfate. After filtration, p-chloroaniline (2.56 g) [mw. 127.57, 20.0 mmol], p-toluenesulfonic acid monohydrate (0.038 g) [mw. 190.22, 0.2 mmol] and cyclohexane (33 mL) were added. Dean-Stark trap was set, and distillation by thermal dehydration was performed for 90 min. After cooling to room temperature, 5 w/w % aqueous acetic acid solution (33 mL) was added to allow for partitioning. The organic layer was washed successively with 5 w/w % aqueous sodium bicarbonate solution (33 mL) and water (33 mL), further washed with water (33 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. To the concentrate were added methanol (q.s.) and activated carbon (1 g), and the mixture was stirred at room temperature for 30 min. After filtration, the mother liquor was concentrated under reduced pressure. The concentrate was purified by basic silica gel column (silica gel amount; 25 g, eluent:toluene, Rf=0.2), and the effective fraction was concentrated under reduced pressure. The concentrate was dissolved in ethyl acetate (3 mL) and diisopropyl ether (30 mL). The mixture was cooled in a freezer to produce crystal core. The mixture was suspended by stirring at room temperature for 1 hr. After filtration under reduced pressure, the crystals were washed with a mixed solvent of ethyl acetate/diisopropyl ether (1/10) (10 mL), and dried at 45° C. under reduced pressure to give the object compound. Pale-yellow white crystal, 2.50 g, yield 31.2%, 1H-NMR (500 MHz, CDCl3, TMS) δ 2.78 (t, J=7.5 Hz, 2H), 3.34 (s, 3H), 3.81 (t, J=8.0 Hz, 2H), 3.99 (s, 2H), 5.29 (s, 2H), 7.03-7.05 (m, 2H), 7.25-7.44 (m, 7H), 10.50 (s, 1H). 13C-NMR (125 MHz, CDCl3, CDCl3) δ 20.95, 43.61, 58.53, 67.71, 67.96, 99.68, 123.83, 128.11, 128.25, 128.57, 129.28, 129.67, 135.81, 138.06, 149.88, 152.23, 169.93.

1. customAfter partitioning
2. washthe organic layer was washed with water (33 mL)
3. dry with materialdried over magnesium sulfate
4. additionwere added
5. distillationdistillation by thermal dehydration
6. waitwas performed for 90 min
7. temperatureAfter cooling to room temperature
8. additionwas added
9. customfor partitioning
10. washThe organic layer was washed successively with 5 w/w % aqueous sodium bicarbonate solution (33 mL) and water (33 mL)
11. washfurther washed with water (33 mL)
12. dry with materialdried over magnesium sulfate
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. additionTo the concentrate were added methanol (q.s.) and activated carbon (1 g)
16. stirringthe mixture was stirred at room temperature for 30 min
17. filtrationAfter filtration
18. concentrationthe mother liquor was concentrated under reduced pressure
19. customThe concentrate was purified by basic silica gel column (silica gel amount; 25 g, eluent:toluene, Rf=0.2)
20. concentrationthe effective fraction was concentrated under reduced pressure
21. dissolutionThe concentrate was dissolved in ethyl acetate (3 mL)
22. temperatureThe mixture was cooled in a freezer
23. customto produce crystal core
24. stirringby stirring at room temperature for 1 hr
25. filtrationAfter filtration under reduced pressure
26. washthe crystals were washed with a mixed solvent of ethyl acetate/diisopropyl ether (1/10) (10 mL)
27. customdried at 45° C. under reduced pressure
28. customto give the object compound

ORD record

ord-cb4e6bb007f6435eb85a9ef8e00c3975

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238667B2