反应详情

A suspension of N-methyl-4-toluamide (100 g) in anhydrous tetrahydrofuran (2 l) was cooled to -28° and n-butyl lithium (580 ml of 2.5M solution in hexanes) was added dropwise maintaining the temperature at -20° to -25°. The resultant solution was stirred at -20° for 2 h, then cooled to -42° and acetone (175 ml) added dropwise maintaining the temperature below -42°. Stirring was continued at -35° to -42° for 1 h before glacial acetic add (39 ml) was added. The mixture was stirred without further cooling for 90 min and then poured into aqueous HCl (1N, 1.4 l) and ethyl acetate (0.5 l). The organic phase was washed with brine (3'1 l), dried over sodium sulphate and concentrated and dried in vacuo. The solid was dissolved in hot methylene chloride (350 ml) and cooled to 3°. The filtrate was treated with hexane (50 ml) and cooled to 3°. The filtrate was dissolved in methylene chloride (1 l) and heated to reflux in the presence of aqueous HCl(6N, 1 l) for 6 h. The organic phase was separated and again heated to reflux in the presence of aqueous HCl (6N, 1 l) for 7 h. The organic phase was separated and washed with saturated aqueous sodium bicarbonate (2'1 l) and concentrated in vacuo to give 3,3,5-trimethyl-3H-isobenzofuran-1-one. HPLC and NMR data were consistent with the product obtained in Preparation A (a) and with its structure.

1. temperaturewas cooled to -28°
2. temperaturemaintaining the temperature at -20° to -25°
3. temperaturecooled to -42°
4. temperaturemaintaining the temperature below -42°
5. additionadd (39 ml)
6. additionwas added
7. stirringThe mixture was stirred
8. temperaturewithout further cooling for 90 min
9. washThe organic phase was washed with brine (3'1 l),
10. dry with materialdried over sodium sulphate
11. concentrationconcentrated
12. customdried in vacuo
13. dissolutionThe solid was dissolved in hot methylene chloride (350 ml)
14. temperaturecooled to 3°
15. additionThe filtrate was treated with hexane (50 ml)
16. temperaturecooled to 3°
17. dissolutionThe filtrate was dissolved in methylene chloride (1 l)
18. temperatureheated
19. temperatureto reflux in the presence of aqueous HCl(6N, 1 l) for 6 h
20. customThe organic phase was separated
21. temperatureagain heated
22. temperatureto reflux in the presence of aqueous HCl (6N, 1 l) for 7 h
23. customThe organic phase was separated
24. washwashed with saturated aqueous sodium bicarbonate (2'1 l) and
25. concentrationconcentrated in vacuo