反应详情

温度

-50 °C

A solution of 2,2,6,6,-tetramethylpiperidine (45 mL, 267 mmol) in THF (400 mL) was cooled below −80° C. under N2-atmosphere. n-Butyl lithium (2.5M in hexane, 110 mL, 275 mmol) was added slowly maintaining the temperature of the mixture below −70° C. After complete addition, the reaction mixture was warmed to −50° C. and stirred at this temperature for 30 minutes. The clear solution became turbid indicating the salt formation. It was cooled to −80° C. again and a solution of 2-fluoro-4-methylbenzonitrile (32.4 g, 240 mmol) in THF (150 mL) was slowly added taking care that the temperature of the reaction mixture remained below −70° C. It was then warmed up to −50° C. and stirred for 30 minutes. The mixture was then cooled to −70° C. and a saturated solution of I2 (67 g, 264 mmol) in THF was added slowly maintaining the temperature at −70° C. After complete addition, the mixture was warmed to ambient temperature. It was added to a solution of Na2S2O3 (160 g in 1.5 L of water) and stirred for an hour. The organic part was separated and the aqueous layer was extracted with EtOAc. The organic layers were combined and washed with brine. The organic layer was then dried over Na2SO4 and filtered. The volatiles were evaporated under reduced pressure. The crude product was subjected to vacuum distillation; at about 60° C., excess TMP was removed, at about 100° C., the starting compound 2-fluoro-4-methylbenzonitrile and a small amount of product was removed and, finally at 115° C., pure 2-fluoro-3-iodo-4-methylbenzonitrile was obtained (30 g, 48% yield). MS (M+H)+ 262.

1. temperaturemaintaining the temperature of the mixture below −70° C
2. additionAfter complete addition
3. temperatureIt was cooled to −80° C. again
4. customremained below −70° C
5. temperatureIt was then warmed up to −50° C.
6. stirringstirred for 30 minutes
7. temperatureThe mixture was then cooled to −70° C.
8. temperaturemaintaining the temperature at −70° C
9. additionAfter complete addition
10. temperaturethe mixture was warmed to ambient temperature
11. stirringstirred for an hour
12. customThe organic part was separated
13. extractionthe aqueous layer was extracted with EtOAc
14. washwashed with brine
15. dry with materialThe organic layer was then dried over Na2SO4
16. filtrationfiltered
17. customThe volatiles were evaporated under reduced pressure
18. distillationThe crude product was subjected to vacuum distillation
19. customat about 60° C., excess TMP was removed, at about 100° C.
20. customthe starting compound 2-fluoro-4-methylbenzonitrile and a small amount of product was removed and, finally at 115° C.