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 then gradually warmed to ambient temperature over 6 hours. The mixture was washed with water (50 mL) and then treated with 3.0 M aqueous NaOH (250 mL). This provided copious amounts of precipitate, which went into solution after about 600 mL water was added. The layers were mixed and separated. The alkaline extract was carefully acidified with concentrated HCl (about 50 mL). The solution was extracted with CH2Cl2 (4×200 mL), and 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 was 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 5.0 g (60%) of the desired product as a red/brown solid.

1. temperatureThe solution was cooled to −78° C.
2. temperatureThe reaction mixture was then 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. additionwas 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. additionwas 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-04160bd5c65748a6a01b0dfa15bc73e7

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08895550B2