Reaction #586111

Reaction equation

(2-chloro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydro-2H-pyrimdin-1-yl)-4-fluorobenzoyloxy]-2-methylpropionic acid

N,N-dimethylsulfamide

triethylamine

→

title compound

2-[2-Chloro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-di-hydro-2H-pyrimidin-1-yl)-4-fluorobenzoyloxy]-2-methylpropionic acid N,N-dimethylsulfamide

Solvents

thionyl chloride

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   Temperaturethe reaction mixture was heated
2. 2
   Temperatureunder reflux for 3 hours
3. 3
   Concentrationthe resulting solution of the acid chloride was then concentrated
4. 4
   workup.ADDITIONwas then added dropwise
5. 5
   Concentrationconcentrated
6. 6
   workup.DISSOLUTIONthe residue was then dissolved in ethyl acetate
7. 7
   WashThe organic phase was washed with 10% strength hydrochloric acid and water
8. 8
   Dryingthe organic phase was dried over sodium sulfate
9. 9
   Filtrationthe drying agent was filtered off
10. 10
    Concentrationthe filtrate was concentrated

Procedure

0.65 g (1.4 mmol) of 2-[(2-chloro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydro-2H-pyrimdin-1-yl)-4-fluorobenzoyloxy]-2-methylpropionic acid from example 4.2 was dissolved in 30 ml of thionyl chloride, the reaction mixture was heated under reflux for 3 hours and the resulting solution of the acid chloride was then concentrated. 0.18 g (1.4 mmol) of N,N-dimethylsulfamide, 0.07 g (1.4 mmol) of 4-dimethylaminopyridine and 0.35 ml (3.5 mmol) of triethylamine were dissolved in 10 ml of dichloromethane, and a solution of the acid chloride which had been prepared beforehand in 10 ml of dichloromethane was then added dropwise. The solution was stirred for 16 hours and then concentrated, and the residue was then dissolved in ethyl acetate. The organic phase was washed with 10% strength hydrochloric acid and water, the organic phase was dried over sodium sulfate, the drying agent was filtered off and the filtrate was concentrated. Column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 2:1) gave 0.30 g of the title compound of melting point 211-213° C.

Source