Dimethylformamide → 2-Chloro-6,8-difluoroquinoline

Temperature

70 °C

6,8-Difluoroquinolin-2-ol (9.89 g, 54.6 mmol) was slurried in 1,2-dichloroethane (550 mL) and treated with DMF (1 mL), and then 2M oxalyl chloride in CH2Cl2 (81.9 mL, 164 mmol) was added dropwise. The reaction was heated to 70° C. for 1 hour and then cooled and concentrated in vacuo. The residue was dissolved in CHCl3 and washed with 50% saturated NaHCO3. The aqueous layer (pH 8) was washed twice with CHCl3 and the combined organics were dried over Na2SO4 and charcoal, filtered, and concentrated in vacuo to a brown solid. The solid was purified by recrystallization from hot hexanes and 1,2-dichloroethane (minimum volume). The solid was collected, washed with hexanes and air-dried to provide the desired product as an off-white solid (5.78 g).

1. temperaturecooled
2. concentrationconcentrated in vacuo
3. dissolutionThe residue was dissolved in CHCl3
4. washwashed with 50% saturated NaHCO3
5. washThe aqueous layer (pH 8) was washed twice with CHCl3
6. dry with materialthe combined organics were dried over Na2SO4 and charcoal
7. filtrationfiltered
8. concentrationconcentrated in vacuo to a brown solid
9. customThe solid was purified by recrystallization from hot hexanes and 1,2-dichloroethane (minimum volume)
10. customThe solid was collected
11. washwashed with hexanes
12. customair-dried

ORD record

ord-5f748ff726dd48e9b6d3fb45fa740469

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08987251B2