Acetonitrile → HCID 67576945, compound

Temperature

20 °C

2-Bromo-2-(2,4-difluorophenyl)-1-bromopropane (3) (20.0 g, 63.7 mmol) was dissolved in acetonitrile (300 mL) at 20° C. and K2CO3 (17.6g, 127 mmol) was added in one portion with efficient stirring. The reaction mixture was heated to reflux for 11 hours and then cooled to 20° C. 1,2,4-Triazole (8.80 g, 127 mmol) was added with stirring and the mixture was heated to reflux for 2 hours. The reaction mixture was cooled to 20° C. and filtered, and 175 mL of acetonitrile was removed by evaporation. The solution was cooled (5° C.) and treated dropwise with a solution of KMnO4 (10.07 g, 63.7 mmol) in water (300 mL) over 45 minutes. After the addition, the black precipitate was removed by filtration through Celite at 20° C. and the filtrate was treated with NaHSO3 (7.2 g) with stirring. The aqueous layer was separated, saturated with NaCl, and extracted with EtOAc (3×400 mL). The combined organic layers were washed with saturated NaHCO3 solution (2×300 mL), and dried over Na2SO4. The aqueous solution was evaporated to half volume and extracted with EtOAc (2×600 mL). Evaporation of the combined EtOAc layers left a crude product which was chromatographed on silica gel (EtOAc/hexanes/EtOH 15:5:1) afforded 27% of 6 as a white crystalline powder.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 11 hours
3. temperaturethe mixture was heated
4. temperatureto reflux for 2 hours
5. temperatureThe reaction mixture was cooled to 20° C.
6. filtrationfiltered
7. custom175 mL of acetonitrile was removed by evaporation
8. temperatureThe solution was cooled (5° C.)
9. additionAfter the addition
10. customthe black precipitate was removed by filtration through Celite at 20° C.
11. additionthe filtrate was treated with NaHSO3 (7.2 g)
12. stirringwith stirring
13. customThe aqueous layer was separated, saturated with NaCl
14. extractionextracted with EtOAc (3×400 mL)
15. washThe combined organic layers were washed with saturated NaHCO3 solution (2×300 mL)
16. dry with materialdried over Na2SO4
17. customThe aqueous solution was evaporated to half volume
18. extractionextracted with EtOAc (2×600 mL)
19. customEvaporation of the combined EtOAc layers
20. waitleft a crude product which
21. customwas chromatographed on silica gel (EtOAc/hexanes/EtOH 15:5:1)

ORD record

ord-4b7523b1bc6a47c699de0359598fc906

Source dataset

uspto-grants-1997_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05633386