反应详情

In a 3 L, 3-neck RBF equipped with mechanical stir, thermocouple and N2 inlet, 90 g (0.455 mol) of 5-chloroisatoic anhydride was suspended in anhydrous THF (0.9 L). Under N2, 4-methoxybenzylchloride (75 g, 0.48 mol) was added followed by the addition of tetrabutylammonium iodide (84 g, 0.23 mol). The reaction mixture was stirred for 5 min at room temperature and then 20 g (0.5 mol) of NaH was added portion-wise over 20 min (reaction temperature increased to 29° C. due to an exotherm and therefore reaction mixture was placed into water bath to keep the temperature below 30° C.). Reaction was stirred for 16 h (RT). Next day HPLC showed about 26% unreacted 5-chloroisatoic anhydride. Additional NaH (1 g) was added and the reaction mixture was heated to 32° C. and stirred for another 5 h. NMR showed that all of the starting material had been consumed. Reaction was quenched by adding 10 g of glacial acetic acid slowly followed by stirring for 30 min. Reaction mixture was filtered through celite and filter cake was washed with THF. Filtrate was concentrated to give 280 g of crude product (yellow-brown solid), which was used with no further purification. 1H NMR (300 MHz, DMSO-d6) δ 3.8 (s, 3H), 5.25 (s, 2H), 6.8 (d, 2H), 7.2 (m, 3H), 7.75 (d, 1 H), 7.9 (d, 1H).

1. customreaction temperature
2. temperatureincreased to 29° C. due to an exotherm
3. customreaction mixture
4. customwas placed into water bath
5. customthe temperature below 30° C.
6. customReaction
7. stirringwas stirred for 16 h (RT)
8. temperaturethe reaction mixture was heated to 32° C.
9. stirringstirred for another 5 h
10. customhad been consumed
11. customReaction
12. customwas quenched
13. additionby adding 10 g of glacial acetic acid
14. stirringby stirring for 30 min
15. customReaction mixture
16. filtrationwas filtered through celite
17. filtrationfilter cake
18. washwas washed with THF
19. concentrationFiltrate was concentrated