反应详情

温度

0 °C

A solution of 2-(2-fluorophenyl)-3-(4-methylthiophenyl)propenoic acid from Step 1 (7.86 g, 27.3 mmol) and triethylamine (2.80 g, 27.7 mmol) in 22 mL of anhydrous toluene was cooled to 0° C. and treated with diphenylphosphoryl azide (7.73 g, 28.1 mmol). The solution was stirred at 0° C. for 20 minutes and at room temperature for 3.50 hours. The reaction was poured into water, extracted with ether, dried over magnesium sulfate, and concentrated in vacuo to remove the ether. The remaining toluene solution was heated to reflux and a vigorous evolution of gas occurred. After 0.75 hours, 11 mL of tert-butyl alcohol was added to the reaction. After an additional twenty minutes, concentrated hydrochloric acid (5 mL) was added slowly and the reaction was heated at 90 ° C. overnight (14 hours). The solution was cooled to room temperature and diluted with ethyl acetate, washed with saturated aqueous NaHCO3, brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo to provide a brown solid that was purified by crystallization from ether to afford 1-(2-fluorophenyl)-2-(4-methylthiophenyl)ethanone as a yellow solid (4.60 g, 65%): mp 58°-59.5° C. 1H NMR (CDCl3) 300 MHz 7.84 (m, 1H), 7.52 (m, 1H), 7.23-7.08 (m, 6H), 4.25 (d, J=2.6Hz, 2H), 2.46 (s, 3H). 19F NMR (CDCl3) -108.51 (m). Mass spectrum M+H+ =261.

1. extractionextracted with ether
2. dry with materialdried over magnesium sulfate
3. concentrationconcentrated in vacuo
4. customto remove the ether
5. temperatureThe remaining toluene solution was heated
6. temperatureto reflux
7. waitAfter 0.75 hours
8. addition11 mL of tert-butyl alcohol was added to the reaction
9. waitAfter an additional twenty minutes
10. additionconcentrated hydrochloric acid (5 mL) was added slowly
11. temperaturethe reaction was heated at 90 ° C. overnight (14 hours)
12. temperatureThe solution was cooled to room temperature
13. additiondiluted with ethyl acetate
14. washwashed with saturated aqueous NaHCO3, brine
15. dry with materialdried over anhydrous MgSO4
16. filtrationfiltered
17. concentrationconcentrated in vacuo
18. customto provide a brown solid that
19. customwas purified by crystallization from ether