Water → HCID 57680938, compound

Temperature

0 °C

Into a solution of 6-chloro-7-methylquinoline (1000 mg, 5.644 mmol) in THF (5 mL), which was cooled in ice/water bath under N2, was added PhLi (1.9 M in THF, 2.971 mL) dropwise over 5 min. After stirring at 0° C. for 15 min, the ice/water bath was removed and the reaction mixture was stirred at rt. After 4 h, MeOH (5 mL) was added to quench the reaction and the reaction mixture was stirred at rt overnight. After that time, the mixture was poured into water (20 mL) and extracted with EtOAc (3×30 mL). The organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in acetonitrile (30 mL) and DDQ (1282 mg) was added and the solution was stirred under N2 at rt for 24 h. After that time, the reaction mixture was poured into aqueous NaOH (3 N, 50 mL) and extracted with EtOAc (2×75 mL). The extracts were washed with aqueous NaOH (3N, 2×50 mL), water (2×50 mL) and brine (50 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford the title compounds; 1H NMR (CDCl3, 400 MHz) δ 2.60 (s, 3H), 7.47-7.55 (m, 3H), 7.83-7.86 (m, 2H), 8.04 (s, 1H), 8.10-8.16 (m, 3H); MS(ES): 254.1/256.1 (M/M+2).

1. customthe ice/water bath was removed
2. stirringthe reaction mixture was stirred at rt
3. waitAfter 4 h
4. additionMeOH (5 mL) was added
5. customto quench
6. customthe reaction
7. stirringthe reaction mixture was stirred at rt overnight
8. extractionextracted with EtOAc (3×30 mL)
9. dry with materialThe organic extracts were dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. dissolutionThe residue was dissolved in acetonitrile (30 mL)
13. additionDDQ (1282 mg) was added
14. stirringthe solution was stirred under N2 at rt for 24 h
15. additionAfter that time, the reaction mixture was poured into aqueous NaOH (3 N, 50 mL)
16. extractionextracted with EtOAc (2×75 mL)
17. washThe extracts were washed with aqueous NaOH (3N, 2×50 mL), water (2×50 mL) and brine (50 mL)
18. dry with materialdried over MgSO4
19. filtrationfiltered
20. concentrationconcentrated in vacuo

ORD record

ord-3be3f1cb2fff48d29366650b1e89f114

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653268B2