Hydrochloric Acid → HCID 131734542, compound

Temperature

25 °C

Into a 100 mL eggplant-shaped flask were added benzyl 3-(2-methoxyacetyl)-2-oxopyrrolidine-1-carboxylate potassium salt (4.95 g) [mw. 329.39, 15.0 mmol], 1 mol/L hydrochloric acid (25 mL) [25 mmol] and toluene (50 mL), and the mixture was stirred for 20 min. After partitioning, the organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. To the concentrate were added toluene (19 mL), cyclohexane (57 mL), p-toluenesulfonic acid monohydrate (29.0 mg) [mw. 190.22, 0.15 mmol] and parabromoaniline (2.58 g) [mw. 172.02, 15.0 mmol]. Dean-Stark trap was set, and the mixture was subjected to dehydration reflux for 2 hr. After cooling to 25° C., 5 w/w % aqueous sodium bicarbonate solution (10 mL) was added to allow for partitioning. The organic layer was washed with water (10 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. To the concentrate was added methanol (19 mL), and the mixture was dissolved. Activated carbon (0.5 g) was added, and the mixture was stirred. The activated carbon was filtered off, the mother liquor was concentrated under reduced pressure, and to the concentrate were added ethyl acetate (2 mL) and diisopropyl ether (20 mL). The mixture was left standing in a freezer at −16° C. overnight, and crystallization was confirmed. The mixture was aged at room temperature for 1 hr. After filtration under reduced pressure, the crystals were washed with ethyl acetate/diisopropyl ether (1/10), and dried under reduced pressure at 50° C. Yellow crystals, 4.12 g, yield 61.6%, 1H-NMR (500 MHz, CDCl3, TMS) δ 2.78 (t, J=7.7 Hz, 2H), 3.35 (s, 3H), 3.76-3.89 (m, 2H), 4.00 (s, 2H), 5.30 (s, 2H), 6.99 (d, J=8.8 Hz, 5H), 7.28-7.52 (m, 7H), 10.49 (s, 1H). 13C-NMR (125 MHz, CDCl3, CDCl3) δ 20.95, 43.60, 58.55, 67.74, 67.97, 99.87, 117.24, 124.08, 128.13, 128.58, 132.24, 135.78, 138.56, 149.72, 152.24, 169.92.

1. customAfter partitioning
2. dry with materialthe organic layer was dried over magnesium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. temperaturereflux for 2 hr
6. additionwas added
7. customfor partitioning
8. washThe organic layer was washed with water (10 mL)
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. additionTo the concentrate was added methanol (19 mL)
13. dissolutionthe mixture was dissolved
14. additionActivated carbon (0.5 g) was added
15. stirringthe mixture was stirred
16. filtrationThe activated carbon was filtered off
17. concentrationthe mother liquor was concentrated under reduced pressure
18. additionto the concentrate were added ethyl acetate (2 mL) and diisopropyl ether (20 mL)
19. waitThe mixture was left
20. waitstanding in a freezer at −16° C. overnight
21. customcrystallization
22. waitThe mixture was aged at room temperature for 1 hr
23. filtrationAfter filtration under reduced pressure
24. washthe crystals were washed with ethyl acetate/diisopropyl ether (1/10)
25. customdried under reduced pressure at 50° C

ORD record

ord-0a005c222d98486f859617babe5f09e0

Source dataset

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09238667B2