反应详情

温度

133 °C

A mixture of 388.2 g (1-methylethyl)-2-[(butylaminocarbonyl)aminosulfonyl]-4-chlorobenzoate and 3 L of xylene was azeotropically dried, then cooled to ~100° C. and 1.0 g of 1,8-diazabicyclo[2.2.2.]octane was added. The mixture was heated to ~141° C. and the addition of liquefied phosgene was begun. After 90 ml of phosgene had been added, the reaction temperature was 128° C. The temperature had risen to 132° C. after 1 hr., and an additional 10 ml phosgene was added. Heating was continued the remainder of the day, then the reaction mixture was allowed to cool overnight under a nitrogen atmosphere. The following morning, the reaction mixture was heated to reflux (133° C.) and 24 ml of phosgene was added over 1 hr. The mixture was heated an additional 2 hrs. (temperature--124° C.) and then cooled to ambient temperature. The reaction mixture was filtered under nitrogen, and the filtrate was concentrated in vacuo. The title compound (400.1 g) was isolated as an oil of sufficient purity for the subsequent coupling reaction.

1. customwas azeotropically dried
2. temperaturecooled to ~100° C.
3. addition]octane was added
4. temperatureThe mixture was heated to ~141° C.
5. additionthe addition of liquefied phosgene
6. additionAfter 90 ml of phosgene had been added
7. customwas 128° C
8. addition, and an additional 10 ml phosgene was added
9. temperatureHeating
10. temperatureto cool overnight under a nitrogen atmosphere
11. temperatureThe following morning, the reaction mixture was heated
12. additionwas added over 1 hr
13. temperatureThe mixture was heated an additional 2 hrs
14. temperature(temperature--124° C.) and then cooled to ambient temperature
15. filtrationThe reaction mixture was filtered under nitrogen
16. concentrationthe filtrate was concentrated in vacuo