Water → 5,6-Dichloro-2-cyclopropylpyrimidine-4-carboxylic acid

Temperature

90 °C

Phosphorus oxychloride (363 g, 221 mL, 2.37 mol) and 5-chloro-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidinecarboxylic acid (169 g, 0.79 mol) were added to a 1-L flask and heated at 90° C. for 5 h. The reaction mixture was cooled to 30° C. and added over 60 minutes into a 2-L jacketed reactor containing a well-stirred mixture of t-butanol (280 mL) and water (750 mL) while maintaining the temperature at 5-10° C. After the addition of the reaction mixture was about 70% complete, the aqueous t-butanol mixture was seeded to initiate crystallization, and the addition of the reaction mixture was continued. At the end of the addition, water (750 mL) was added gradually at 10-15° C., and the mixture was stirred for an additional 1 h. The resulting mixture was cooled to 5° C., filtered, and the collected solid was washed with water (3×50 mL). The resulting wet cake was dried in a vacuum-oven at 60° C. to give 156 g (85% yield) of the title compound as a solid melting at 126-127° C.

1. temperatureThe reaction mixture was cooled to 30° C.
2. additionadded over 60 minutes into a 2-L jacketed reactor
3. additioncontaining
4. temperaturewhile maintaining the temperature at 5-10° C
5. additionAfter the addition of the reaction mixture
6. customcrystallization
7. additionthe addition of the reaction mixture
8. additionAt the end of the addition, water (750 mL)
9. additionwas added gradually at 10-15° C.
10. temperatureThe resulting mixture was cooled to 5° C.
11. filtrationfiltered
12. washthe collected solid was washed with water (3×50 mL)
13. customThe resulting wet cake was dried in a vacuum-oven at 60° C.

ORD record

ord-2adaef1bdf29442aab31bf7e69e1ff01

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08198442B2