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 bi-phasic solution was cooled to 0-5° C. Cl2 gas was slowly purged through the reaction mixture for 5 minutes and was allowed to stir at room temperature for 30 minutes. The reaction mixture was diluted with water (10 mL) and extracted with 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 Condition B-81: 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. customCl2 gas was slowly purged through the reaction mixture for 5 minutes
2. additionThe reaction mixture was diluted with water (10 mL)
3. extractionextracted with CCl4 (100 mL)
4. customThe organic layer was separated
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe resulting residue was dissolved in dry THF (5 mL)
9. temperatureThe reaction mixture was heated in a sealed tube at 60° C. for 6 h
10. temperatureto cool to ambient temperature
11. customThe solution was transferred to a separation funnel
12. washwashed with water (50 mL)
13. dry with materialThe organic layer was dried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under reduced pressure
16. customThe resulting residue was purified by CombiFlash Isco (REDISEP®, SiO2, 40 g, 0-15% EtOAc/petroleum ether)

ORD record

ord-f0b10babeb7a4afe9af9368795dfe067

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09050345B2