反应详情

A solution of 8.0 g (25 mmol) of 2-[4'-[(difluoromethyl)thio][1,1'-biphenyl]-4-yl]-2-methyl-1,3-dioxolane and 30 mL of anhydrous 1,2-dichloroethane was cooled to 5° C. and sulfuryl chloride (2.3 mL, 3.8 g, 28 mmol) was added via syringe. The solution was allowed to warm to ambient temperature and concentrated to dryness. Acetone (40 mL), 5 mL of water, and 2 mL of 37% HCl were added, and the mixture was heated at 55° C. for 18 h. The mixture was diluted with 20 mL of water with cooling and seeding to precipitate the product. After filtration, washing with cold 50% aqueous MeOH and drying, the crude solid (7.2 g, 92%) was slurried in 80 mL of hot isopropanol (i-PrOH) allowed to cool with good stirring for 30 min, and filtered to afford 5.6 g of 2-chloro-1-[4'-[(difluoro-methyl)thio][1,1'-biphenyl]-4-yl]ethanone, m.p. 102-104° C. A second crop of 0.9 g was obtained by partial concentration of the filtrate. An analytical standard was prepared by chromatography and/or recrystallization from CH2Cl2 /MeOH, m.p. 104 to 105° C. 1H-NMR(CDCl3): δ4.75 (s, 2H), 6.88 (t, 1H), 7.65 (ABq, 4H) 7.7 (d, A of ABq, 2H), 8.05 (d, B of ABq, 2H).

1. concentrationconcentrated to dryness
2. additionAcetone (40 mL), 5 mL of water, and 2 mL of 37% HCl were added
3. temperaturethe mixture was heated at 55° C. for 18 h
4. additionThe mixture was diluted with 20 mL of water
5. temperaturewith cooling
6. customto precipitate the product
7. filtrationAfter filtration
8. washwashing with cold 50% aqueous MeOH
9. customdrying
10. temperatureto cool
11. filtrationfiltered