反应详情

温度

10 °C

A reaction vessel was charged with POCl3 (1500.0 g, 9.78 mol). Br2 (184.9 g, 1.157 mol) was then added in one portion at ambient temperature. The reaction mixture was cooled to 10° C. and then PBr3 (313.0 g, 1,157 mol) was added over 25 min. under vigorous stirring. The temperature of the reaction mixture increased to 20° C. After addition, stirring was continued for another 1.5 h, maintaining the temperature in the range of 10–20° C. The formed PBr5 precipitated as a yellow solid. The reaction mixture was warmed to 25° C. and 1,3-dihydro-1-(3-phenylpropyl)-4-(4-fluorophenyl)-5-(4-pyridyl)-imidazol-2-one (150.0 g 0,386 mol) was added in one portion. After addition, the reaction mixture was heated to about 30° C. and stirring was continued for 24 h. The suspension changed to a dark solution. The POCl3 was distilled off under vacuum at a temperature below 35° C., to yield a viscous oil. This oil was added to a mixture of ethyl acetate (1000 g) and aqueous ammonia (25 w %, 1000 g) over about 1.25 hours, with cooling. The resulting two phases were separated, the aqueous phase was extracted with ethyl acetate (500 g) and the combined organic phases were washed with water (200 g) at 70° C. The organic phase was concentrated to approximately 30% of the original volume. To the warmed reaction mixture, was then added triethylamine (600 g) and an additional amount of the solvent (about 150 g) was removed in vacuo, resulting in the crystallization of the desired product. The reaction mixture was cooled to 0° C. and stirred for 12 h. The product was filtered off, washed with triethylamine (50 g) and dried at 40° C. under vacuum, to yield the crude product.

1. temperatureThe temperature of the reaction mixture increased to 20° C
2. additionAfter addition
3. temperaturemaintaining the temperature in the range of 10–20° C
4. customThe formed PBr5 precipitated as a yellow solid
5. temperatureThe reaction mixture was warmed to 25° C.
6. additionAfter addition
7. temperaturethe reaction mixture was heated to about 30° C.
8. stirringstirring
9. waitwas continued for 24 h
10. distillationThe POCl3 was distilled off under vacuum at a temperature below 35° C.
11. customto yield a viscous oil
12. temperaturewith cooling
13. customThe resulting two phases were separated
14. extractionthe aqueous phase was extracted with ethyl acetate (500 g)
15. washthe combined organic phases were washed with water (200 g) at 70° C
16. concentrationThe organic phase was concentrated to approximately 30% of the original volume
17. customTo the warmed reaction mixture
18. customadded triethylamine (600 g) and an additional amount of the solvent (about 150 g) was removed in vacuo