99-43-4

ChEBI: A benzoate ester in which 4-amino-3-butoxybenzoic acid and 2-(diethylamino)ethanol have combined to form the ester bond; an ester-based local anaesthetic (ester "caine") used especially in ophthalmology and otolaryngology.

Dorsacaine HCl,Dorsey,US,1953

Anesthetic (topical).

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.

Dorsacaine (Novartis).

Local anesthetic