Phosphorus oxychloride → 5,6-Dichloro-2-cyclopropylpyrimidine-4-carboxylic acid

Temperature

90 °C

Phosphorus oxychloride (200 mL, 328 g, 2.14 mol) and 5-chloro-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidinecarboxylic acid (i.e. the product of Step B1 or B2) (96.8 g, 451 mmol) were combined and heated at 90° C. for 5 h. The reaction mixture was cooled to 50-60° C. and concentrated at reduced pressure to half volume. After cooling to 30° C. the reaction mixture was added over 60 minutes to a mixture of t-butanol (200 mL) and water (300 mL), with the temperature maintained at 8-10° C. The mixture was seeded, water (300 mL) was added gradually at 10-15° C. and the mixture was stirred for 1 h. After cooling to 5° C. the precipitated product was isolated by filtration and washed with water (3×50 mL). The solid was dried in a vacuum oven to afford the title compound (93 g).

1. temperatureThe reaction mixture was cooled to 50-60° C.
2. concentrationconcentrated at reduced pressure to half volume
3. temperatureAfter cooling to 30° C. the reaction mixture
4. additionwas added over 60 minutes to a mixture of t-butanol (200 mL) and water (300 mL), with the temperature
5. temperaturemaintained at 8-10° C
6. additionwater (300 mL) was added gradually at 10-15° C.
7. temperatureAfter cooling to 5° C. the precipitated product
8. customwas isolated by filtration
9. washwashed with water (3×50 mL)
10. customThe solid was dried in a vacuum oven

ORD record

ord-cfdf4184cd4940c4b595f49faebd3e9a

Source dataset

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07863220B2