Originator
Corindolan,Schering,W. Germany,1980
Manufacturing Process
The 4-hydroxy-2-methylindole (MP 112°C to 115°C from benzene/ethyl acetate), used as starting material, may be obtained by hydrogenation of 4- benzyloxy-2-dimethylamino-methylindole (MP 117°C to 120°C from benzene) in the presence of a palladium catalyst (5% on aluminum oxide).
11.6 g of 4-hydroxy-2-methylindole are added to a solution of 3.1 g of sodium hydroxide in 150 cc of water, and then 12.4 cc of epichlorhydrin are added while stirring and in an atmosphere of nitrogen. The reaction mixture is further stirred at room temperature for 24 hours, is extracted 4 times with methylene chloride, and the combined organic layers which have been dried over magnesium sulfate are concentrated by evaporation at reduced pressure. The resulting residue is taken up in 150 cc of dioxane and 50 cc of isopropylamine, and the mixture is heated to the boil for 6 hours. The reaction mixture is evaporated to dryness at reduced pressure, the residue is shaken 4 times between ethyl acetate and a 1 N aqueous tartaric acid solution, and a 5 N caustic soda solution is then added to the combined tartaric acid phases until an alkaline reaction is obtained. The alkaline solution is then shaken out 6 times with methylene chloride, the combined extracts are dried over magnesium sulfate, and the solvent is evaporated in a vacuum. The oily viscous residue may be crystallized from ethyl acetate. The title compound has a MP of 95°C to 97°C.
