反应详情

温度

120 °C

A 200-ml 4-necked flask equipped with a mechanical stirrer, a thermometer, a distillation head, a vacuum controller, an argon inlet and an oil bath was charged with 24.7 g of crude methyl rac-(E)-4-bromo-3-methoxy-pent-2-enoate (ca. 0.107 mol), 19.91 g of benzamide (0.161 mol) and 57 ml of toluene. The orange suspension was stirred and heated with an oil bath at 120° C. At a still temperature of 111° C. low boiling componentes started to distill. The head temperature reached 103° C. after ca. 1 h and was 65° C. after 6 h. After 9 h the oil bath was removed and the reaction mixture stirred over night at rt. Thereafter the toluene was removed at 60° C. bath temperature and a pressure between 300 and 70 mbar. After cooling to rt, 80 ml of methanol and 0.60 g of p-toluenesulfonic acid monohydrate were added and the brown solution stirred at reflux (ca. 73° C.) for 2 h. Subsequently 2.5 g of charcoal and 50 ml of methanol were added, the mixture was stirred for 30 min, filtered with suction through Dicalite Speedex and rotary evaporated to dryness (50° C., 8 mbar, 30 min). The orange semi-solid residue was treated under argon with 250 ml of toluene and 55 ml of sat. aqueous sodium bicarbonate solution. The resulting suspension was stirred in an ice bath for 0.5 h, the precipitated benzamide was filtered off with suction and the filter cake was washed three times with 50 ml portions, a total of 150 ml of ice cold toluene and with little water. The combined aqueous phases (pH=8)were extracted in a separatory funnel with 80 ml of toluene. Thereafter the combined organic phases were washed twice with 50 ml, a total of 100 ml of deionized water, dried (Na2SO4) and rotary evaporated (50° C., 10 mbar, 1 h) to give 21.8 g of crude Methyl 2-(5-methyl-2-phenyl-4-oxazolyl)acetate (theor. amount 24.7 g) as a red-brown oil, which can be used without purification in subsequent steps.

1. customA 200-ml 4-necked flask equipped with a mechanical stirrer
2. customAt a still temperature of 111° C. low boiling componentes
3. distillationto distill
4. waitwas 65° C. after 6 h
5. customAfter 9 h the oil bath was removed
6. stirringthe reaction mixture stirred over night at rt
7. customThereafter the toluene was removed at 60° C. bath temperature
8. temperatureAfter cooling to rt
9. addition80 ml of methanol and 0.60 g of p-toluenesulfonic acid monohydrate were added
10. stirringthe brown solution stirred
11. temperatureat reflux (ca. 73° C.) for 2 h
12. additionSubsequently 2.5 g of charcoal and 50 ml of methanol were added
13. stirringthe mixture was stirred for 30 min
14. filtrationfiltered with suction through Dicalite Speedex
15. customrotary evaporated to dryness (50° C., 8 mbar, 30 min)
16. additionThe orange semi-solid residue was treated under argon with 250 ml of toluene and 55 ml of sat. aqueous sodium bicarbonate solution
17. stirringThe resulting suspension was stirred in an ice bath for 0.5 h
18. filtrationthe precipitated benzamide was filtered off with suction
19. washthe filter cake was washed three times with 50 ml portions
20. extractionThe combined aqueous phases (pH=8)were extracted in a separatory funnel with 80 ml of toluene
21. washThereafter the combined organic phases were washed twice with 50 ml
22. dry with materiala total of 100 ml of deionized water, dried (Na2SO4)
23. customrotary evaporated (50° C., 10 mbar, 1 h)