Manufacturing Process
20.8 g of 4-hydroxy-3-methoxyacetophenone are dissolved in 350 ml of
dioxane and 350 ml of water by the addition of 30.0 g of sodium hydroxide,
and the resulting solution is heated to 60°C. While stirring continuously,
chlorodifluoromethane is passed into the solution until uptake of the gas stops
(about 4 h). The solution is cooled, and the resulting precipitate is filtered off
with suction and washed three times with 40 ml of diethyl ether each time.
The solution is diluted with water to twice its volume and likewise extracted
three times with 100 ml of diethyl ether each time. The combined ether
extracts are dried over magnesium sulfate and evaporated in vacuum; the
residue is crystallized from petroleum ether (boiling point 50°-70°C), 19.0 g
(70.4% of theory) of 4-difluoromethoxy-3-methoxyacetophenone are
obtained, melting point 68°C.
15.0 g of 4-difluoromethoxy-3-methoxyacetophenone are heated with 5.9 g of
glyoxylic acid monohydrate at 110°C for 2 h. The melt is then cooled to 60°C,
30 ml of water are added, and dissolution is brought about by addition of 10
ml of concentrated aqueous ammonium solution. 3.2 g of hydrazine hydrate
are added, and the mixture is boiled under reflux for 2 h, during which the
title compound gradually crystallizes out. After cooling, the precipitate is
filtered off with suction, thoroughly washed with water, dried and recrystallized from isopropanol. 10.8 g (58.1% of theory) of the 6-(4-
difluoromethoxy-3-methoxyphenyl)-3(2H)pyridazinone are obtained, melting
point 204°C.
