Water → HCID 90386300, compound

3-(Benzylthio)-5-bromo-2-(difluoromethyl)pyridine (0.900 g, 2.73 mmol) was dissolved in CCl4 (75 mL) and water (15 mL) and the resulting biphasic solution was cooled to 0-5° C. Then Cl2 gas was slowly purged through the reaction mixture for 5 minutes and allowed to stir at room temperature for 30 minutes. The reaction mixture was diluted with water (10 mL) and CCl4 (100 mL). The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was dissolved in dry THF (5 mL) and slowly added to 2-methylpropan-2-amine (5.00 mL, 2.73 mmol) at 0-5° C. The reaction mixture was heated in a sealed tube at 60° C. for 6 h, allowed to cool to ambient temperature and diluted with EtOAc (300 mL). The solution was transferred to a separation funnel and washed with water (50 mL) followed by brine solution (25 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was purified by CombiFlash Isco (REDISEP®, SiO2, 40 g, 0-15% EtOAc/petroleum ether) to obtain 5-bromo-N-(tert-butyl)-2-(difluoromethyl)pyridine-3-sulfonamide (0.80 g, 85%) as a brown liquid. LCMS Method B-11: retention time 2.19 min, [M+2]=345.0. 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.15 (s, 9H), 7.59 (t, J=52.8 Hz, 1H), 8.25 (br s, 1H), 8.54 (dd, J=0.8 Hz, J=2.0 Hz, 1H), 9.12 (d, J=2.0 Hz, 1H).

1. customThen Cl2 gas was slowly purged through the reaction mixture for 5 minutes
2. additionThe reaction mixture was diluted with water (10 mL) and CCl4 (100 mL)
3. customThe organic layer was separated
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. dissolutionThe resulting residue was dissolved in dry THF (5 mL)
8. temperatureThe reaction mixture was heated in a sealed tube at 60° C. for 6 h
9. temperatureto cool to ambient temperature
10. customThe solution was transferred to a separation funnel
11. washwashed with water (50 mL)
12. dry with materialThe organic layer was dried over Na2SO4
13. filtrationfiltered
14. concentrationconcentrated under reduced pressure
15. customThe resulting residue was purified by CombiFlash Isco (REDISEP®, SiO2, 40 g, 0-15% EtOAc/petroleum ether)

ORD record

ord-7dba6f55299a4960ad9204733f32b68d

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09403834B2