Ethanol → HCID 178439971, compound

To a solution of 3,5-dimethoxy-2-nitroaniline (55.0 g, 321 mmol) and pyridine (400 mL) was added isobutyryl chloride (41.0 mL, 391 mmol). After stirring for 16 hours, the reaction mixture was concentrated in vacuo. The resulting oil was partitioned between H2O (200 mL) and ethyl acetate (200 mL). The aqueous layer was extracted with more ethyl acetate (2×200 mL). The organic layers were washed with brine (50 mL), dried (MgSO4) and concentrated. The solid was recrystallized from hexane/ethyl acetate at 5° C. to afford yellow crystals. To a slurry of the yellow crystals, 4N HCl (200 mL) and ethanol (250 mL) was added 10% Pd/C (1.30 g). The slurry was placed under 50 psi of H2 (g) and shaken for 4 hours. The mixture was then filtered and concentration of the filtrate afforded a white solid. The white solid was dissolved in 2N HCl (200 mL) and refluxed for 4 hours. The reaction mixture was concentrated. The resulting solid was dissolved in 48% HBr (100 mL) and H2O (100 mL) and refluxed for 15 hours. The reaction was then cooled to ambient temperature and concentrated. The solids were dissolved in H2O (200 mL) and neutralized (KHCO3). The aqueous layer was then extracted with n-butanol (3×500 mL). The organic layer was washed with brine (50 mL), treated with activated charcoal and concentrated to afford 4,6-dihydroxy-2-isopropylbenzimidazole, a compound of formula (11).

1. concentrationthe reaction mixture was concentrated in vacuo
2. customThe resulting oil was partitioned between H2O (200 mL) and ethyl acetate (200 mL)
3. extractionThe aqueous layer was extracted with more ethyl acetate (2×200 mL)
4. washThe organic layers were washed with brine (50 mL)
5. dry with materialdried (MgSO4)
6. concentrationconcentrated
7. customThe solid was recrystallized from hexane/ethyl acetate at 5° C.
8. customto afford yellow crystals
9. stirringshaken for 4 hours
10. filtrationThe mixture was then filtered
11. customconcentration of the filtrate afforded a white solid
12. temperaturerefluxed for 4 hours
13. concentrationThe reaction mixture was concentrated
14. dissolutionThe resulting solid was dissolved in 48% HBr (100 mL)
15. temperatureH2O (100 mL) and refluxed for 15 hours
16. concentrationconcentrated
17. dissolutionThe solids were dissolved in H2O (200 mL)
18. extractionThe aqueous layer was then extracted with n-butanol (3×500 mL)
19. washThe organic layer was washed with brine (50 mL)
20. additiontreated with activated charcoal
21. concentrationconcentrated

ORD record

ord-c29c9f1e6bab485f88c5ac58d821366d

Source dataset

uspto-grants-1998_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05849759