Dimethylformamide → 3-Bromo-4-(difluoromethoxy)pyridine

Temperature

120 °C

To a stirred solution of 3-bromopyridin-4-ol (L); 0.5 g, 0.00287 mol) in mixture of N,N-dimethylformamide (10.0 mL), water (1 mL), was added 2-chloro-2,2-difluoroacetic acid (0.74 g, 0.00574 mol) and potassium carbonate (0.47 g, 0.00344 mol). The resulting mixture was heated under microwave irradiation at 120° C. for 45 min. The reaction mixture was cooled to room temperature and poured into water (10.0 mL) and extracted with ethyl acetate (2×50.0 mL). Combined organic phase was washed with saturated sodium bicarbonate solution, water, saturated aqueous sodium chloride solution, dried over sodium sulphate, filtered and concentrated under vacuum to afford crude product. The crude was purified by silica gel (60-120) column chromatography using 0-8% methanol in dichloromethane to afford the title compound (IN-13). 1H NMR (400 MHz, DMSO-d6) δ: 8.606-8.60 (d, J=2.4 Hz, 1H), 8.08-8.05 (dd, J=5.2 Hz, 1H), 7.67-7.37 (t, J=58.8 Hz, 1H), 6.38-6.36 (dd, J=7.2 Hz, 1H). MS (M+1): 223.8.

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionextracted with ethyl acetate (2×50.0 mL)
3. washCombined organic phase was washed with saturated sodium bicarbonate solution, water, saturated aqueous sodium chloride solution
4. dry with materialdried over sodium sulphate
5. filtrationfiltered
6. concentrationconcentrated under vacuum
7. customto afford crude product
8. customThe crude was purified by silica gel (60-120) column chromatography

ORD record

ord-30d760a25d13452bb2a896f763478ff8

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073929B2