反应详情

温度

100 °C

5-Trifluoromethyluracil (250 g, 1.39 mol) and phosphorous oxychloride (655 mL, 6.94 mol, 5 equiv) were charged to a 3 L 4-neck flask equipped with overhead stirrer, a reflux condenser, an addition funnel and an internal thermocouple. The contents were maintained under a nitrogen atmosphere as concentrated phosphoric acid (85 wt %, 9.5 mL, 0.1 equiv) was added in one portion to the slurry, resulting in a moderate exotherm. Diisopropylethylamine (245 mL, 1.39 mol, 1 equiv) was then added dropwise over 15 min at such a rate that the internal temperature of the reaction reached 85-90° C. by the end of the addition. By the end of the amine addition the reaction mixture was a homogenous light-orange solution. Heating was initiated and the orange solution was maintained at 100° C. for 20 h, at which time HPLC analysis of the reaction mixture indicated that the starting material was consumed. External heating was removed and the contents of the flask were cooled to 40° C. and then added dropwise to a cooled mixture of 3N HCl (5 L, 10 equiv) and diethyl ether (2 L) keeping the temperature of the quench pot between 10 and 15° C. The layers were separated, and the aqueous layer was extracted once with ether (1 L). The combined organic layers were combined, washed with water until the washes were neutral (5×1.5 L washes), dried with MgSO4 and concentrated to provide 288 g (95% yield) of a light yellow-orange oil of 96% purity (HPLC). This material can be further purified by distillation (bp 109° C. at 79 mmHg).

1. customequipped with overhead stirrer, a reflux condenser, an addition funnel
2. additionwas added in one portion to the slurry
3. customresulting in a moderate exotherm
4. additionreached 85-90° C. by the end of the addition
5. temperatureHeating
6. customwas consumed
7. temperatureExternal heating
8. customwas removed
9. temperaturethe contents of the flask were cooled to 40° C.
10. customthe temperature of the quench pot between 10 and 15° C
11. customThe layers were separated
12. extractionthe aqueous layer was extracted once with ether (1 L)
13. washwashed with water until the washes
14. dry with materialdried with MgSO4
15. concentrationconcentrated