Toluene → HCID 21824657, compound

Temperature

-25 °C

To a 250 mL flask was added toluene (150 mL) and t-BuNH2 (7.26 mL, 69.1 mmol). The solution was cooled to −25° C. and bromine (1.95 mL, 38.0 mmol) was added. The solution was cooled to −78° C. and 2-methylquinolin-8-ol (5.5 g, 34.6 mmol) was added as a CH2Cl2 solution (15 mL). The reaction mixture was gradually warmed to ambient temperature over 6 hours. The mixture was washed with water (50 mL) and treated with 3.0 M aqueous NaOH (250 mL). This provided copious amounts of precipitate, which went into solution after about 600 mL water were added. The layers were mixed and separated. The alkaline extract was carefully acidified with concentrated HCl (=50 mL). The solution was extracted with CH2Cl2 (4×200 mL), the combined extracts were washed with brine and dried over Na2SO4, filtered and concentrated. The original water wash was found to contain a significant amount of product, so 10 mL 1M HCl were added and the acidic solution was extracted with CH2Cl2 (2×75 mL) and these layers were also washed with brine, dried over Na2SO4, filtered and concentrated. The organic phases were combined to provide 5.01 g (60%) of the desired product as a red/brown solid.

1. temperatureThe solution was cooled to −78° C.
2. temperatureThe reaction mixture was gradually warmed to ambient temperature over 6 hours
3. washThe mixture was washed with water (50 mL)
4. additiontreated with 3.0 M aqueous NaOH (250 mL)
5. additionwere added
6. additionThe layers were mixed
7. customseparated
8. extractionThe alkaline extract
9. extractionThe solution was extracted with CH2Cl2 (4×200 mL)
10. washthe combined extracts were washed with brine
11. dry with materialdried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. washThe original water wash
15. additionwere added
16. extractionthe acidic solution was extracted with CH2Cl2 (2×75 mL)
17. washthese layers were also washed with brine
18. dry with materialdried over Na2SO4
19. filtrationfiltered
20. concentrationconcentrated

ORD record

ord-cba9702c12ff4e0281e50bcf638a86d0

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987251B2