Reaction #50444

Reaction equation

sodium iodide

potassium carbonate

7-[(4,6-dimethoxy-pyrimidin-2-yl)oxy]-3-hydroxy-phthalide

chloroacetonitrile

18-crown-6

→

3-cyanomethoxy-7-[(4,6-dimethoxy-pyrimidin-2-yl)oxy]-phthalide

Solvents

ethyl methyl ketone

tert-butyl methyl ether

Conditions

Workup

1. 1
   TemperatureWhen the reaction material has cooled
2. 2
   Washthe solution is washed with dilute hydrochloric acid and water
3. 3
   Concentrationconcentrated by evaporation
4. 4
   Otherpurified by chromatography on silica gel (eluant: ethyl acetate/n-hexane 1:1)

Procedure

A mixture of 1.5 g of 7-[(4,6-dimethoxy-pyrimidin-2-yl)oxy]-3-hydroxy-phthalide (see Example 84) and 0.8 ml of chloroacetonitrile is maintained at 60° C. for 1 hour in ethyl methyl ketone in the presence of 2.1 g of dry potassium carbonate and a spatula tip each of sodium iodide and 18-crown-6. When the reaction material has cooled, it is taken up in tert-butyl methyl ether and the solution is washed with dilute hydrochloric acid and water, concentrated by evaporation and purified by chromatography on silica gel (eluant: ethyl acetate/n-hexane 1:1) to yield 3-cyanomethoxy-7-[(4,6-dimethoxy-pyrimidin-2-yl)oxy]-phthalide, m.p. 99°-102° C.

Source