Dorsacaine HCl,Dorsey,US,1953
25 grams of 3-oxy-4-nitrobenzoic acid are esterified (ethyl ester) and 26
grams of the ester are dissolved in 200 cc of absolute ether and treated with
7 grams of caustic potash in 20 cc of absolute methanol. The red potassium
phenolate with 7 grams of pure butyl bromide and 7 grams of absolute alcohol
are heated for 5 hours in the oven to 150°C. When cool, the alcohol is
evaporated in vacuo and the butoxy-nitrobenzoic acid ethyl ester is
precipitated with water. The substance is sucked off and saponified for 15
minutes with a solution of 2.5 grams of caustic potash in 30 cc of alcohol on a
water bath. The alcohol is evaporated in vacuo and the 3-butoxy-4-
nitrobenzoic acid is precipitated with hydrochloric acid. It forms needles which
melt at 174°C. 7.9 grams of dry acid are boiled for 45 minutes under a reflux
condenser with 25 cc of thionyl chloride. The excess of thionyl chloride is then
removed in vacuo, and the oil is distilled. The acid chloride has a yellow color
and solidifies.
7.3 grams of the acid chloride are treated with 6.6 grams of diethyl-aminoethanol
in 20 cc of absolute benzene. The mixture is then warmed for 1 hour
on a water bath. When cold, it is treated with a solution of soda and washed
with ether. After drying over potash, the ether and benzene are removed by
distillation and 3-butoxy-4-nitrobenzoic acid diethylamino-ethyl ester is
obtained, having a BP 215°C/2.5 mm.
5.0 grams of this product are hydrogenated in absolute alcohol solution with
fresh Raney nickel. When the absorption of hydrogen ceases (5 hours), the
solution is filtered and the alcohol evaporated in vacuo. The 3-butoxy-4-
aminobenzoic acid diethyl-amino-ethyl ester boils at 215°-218°C at 2 mm
pressure; it is an almost colorless oil.
By precipitation of a solution of the ester in absolute ether with hydrogen
chloride gas, the dihydrochloride is obtained; upon recrystallization from
alcohol/ether, it forms crystals which melt at 196°-197°C.
