Reaction #336838

Reaction equation

Phosphorus oxychloride

5-chloro-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidinecarboxylic acid

product

5-chloro-2-cyclopropyl-1,6-dihydro-6-oxo-4-pyrimidine-carboxylic acid

→

title compound

5,6-dichloro-2-cyclopropyl-4-pyrimidinecarboxylic acid

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was cooled to 50-60° C.
2. 2
   Concentrationconcentrated at reduced pressure to half volume
3. 3
   TemperatureAfter cooling to 30° C. the reaction mixture
4. 4
   workup.ADDITIONwas added over 60 minutes to a mixture of t-butanol (200 mL) and water (300 mL), with the temperature
5. 5
   Temperaturemaintained at 8-10° C
6. 6
   workup.ADDITIONwater (300 mL) was added gradually at 10-15° C.
7. 7
   TemperatureAfter cooling to 5° C. the precipitated product
8. 8
   Otherwas isolated by filtration
9. 9
   Washwashed with water (3×50 mL)
10. 10
    OtherThe solid was dried in a vacuum oven

Procedure

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).

Source