反应详情

温度

22 °C

DCM (350 ml, 1 L/mol) was added to 91.7 g 5-iodo-2-methylbenzoic acid (91.7 g, 0.35 mol) and the resulting heterogeneous mixture stirred at 22° C. To the resulting mixture was then added thionyl chloride (42.5 g, 0.35 mol) via an addition funnel. The resulting mixture was warmed slowly to reflux temperature (over which time the mixture became a colorless solution and gas evolution was observed), then stirred for 1 hr, then cooled to 2° C. Aluminum chloride granules (56.0 g, 0.42 mol) were added to the resulting mixture, which was then stirred for 15 min at 2° C. A solution of 2-(4-fluorophenyl)thiophene (0.35 mol, 89.7% w/w) in DCM (0.5 L/mol) was then added via addition funnel over 10 minutes, allowing the temperature to rise during addition to 20° C. The resulting mixture was stirred at 20° C. for 2 hrs, then cooled to 2° C. Additional aluminum chloride granules (107.3 g, 0.805 mol) were added and the resulting mixture stirred for 15 min. Acetonitrile (210 ml, 0.6 L/mol) was added via addition funnel over 20 minutes at T≦20° C. Tetramethyldisiloxane (131.6 g, 0.98 mol) was then added via addition funnel over 5 minutes. The resulting mixture was slowly warmed to reflux temperature (42° C.), maintained at reflux for 3 hours, allowed to cool to 22° C. and then stirred for 16 hrs. Water (420 ml, 1.2 L/mol) was added over 30 minutes at T≦35° C. and the resulting mixture stirred strongly for 15 min. The resulting layers were separated, the organic layer washed with water (70 ml, 0.2 L/mol), then concentrated in vacuo at 50° C. to yield the title compound as a residue.

1. temperatureThe resulting mixture was warmed slowly
2. temperatureto reflux temperature (over which time the mixture
3. stirringthen stirred for 1 hr
4. temperaturecooled to 2° C
5. stirringwas then stirred for 15 min at 2° C
6. additionto rise during addition to 20° C
7. stirringThe resulting mixture was stirred at 20° C. for 2 hrs
8. temperaturecooled to 2° C
9. stirringthe resulting mixture stirred for 15 min
10. temperatureThe resulting mixture was slowly warmed
11. temperatureto reflux temperature (42° C.)
12. temperaturemaintained
13. temperatureat reflux for 3 hours
14. temperatureto cool to 22° C.
15. stirringstirred for 16 hrs
16. stirringthe resulting mixture stirred strongly for 15 min
17. customThe resulting layers were separated
18. washthe organic layer washed with water (70 ml, 0.2 L/mol)
19. concentrationconcentrated in vacuo at 50° C.