Phosphorus oxychloride → 4-Chloro-6-ethyl-5-fluoropyrimidine

Temperature

25 °C

To a mixture of the compound of part (iv) (40 kg), dichloromethane (120 L) and triethylamine (28.4 g) was slowly added phosphorus oxychloride (47.2 kg) over 3 hours maintaining the reaction temperature below 40° C. during the addition. The mixture was heated under reflux for 5 hours, cooled to 25° C. and cautiously quenched into 3N aqueous hydrochloric acid solution (176 L), maintaining the temperature below 20° C. during this operation. The layers were separated, the aqueous phase extracted with dichloromethane (50 L) and the combined organic layers washed with water (50 L). The organic layer was concentrated under reduced pressure to provide the product as an oil (40.69 kg).

1. customover 3 hours
2. temperaturemaintaining the reaction temperature below 40° C.
3. additionduring the addition
4. temperatureThe mixture was heated
5. temperatureunder reflux for 5 hours
6. customcautiously quenched into 3N aqueous hydrochloric acid solution (176 L)
7. temperaturemaintaining the temperature below 20° C. during this operation
8. customThe layers were separated
9. extractionthe aqueous phase extracted with dichloromethane (50 L)
10. washthe combined organic layers washed with water (50 L)
11. concentrationThe organic layer was concentrated under reduced pressure

ORD record

ord-acda1c869114481394084676416337bc

Source dataset

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06946555B2