[R-(R*,S*)]-1-cyclohexyl-3-[(2-hydroxy-1-methyl-2-phenylethyl)amino]propan-1-one hydrochloride

Alifedrine hydrochloride,Chemiewerk Homberg

There are some means to produce aliflurane:
1). 2.2 g (0.01 mol) of (2-dimethylaminoethyl)cyclohexylketone hydrochloride (produced by Mannich reaction from 1-acetyl-1-cyclohexene with formaldehyde and dimethylamine hydrochloride and subsequent hydrogenation with Pd/C as catalyst) and 1.5 g (0.01 mol) of 1-norephedrine were dissolved in 20 ml of warm isopropanol. The product crystallizing out in the cooling was filtered off with suction and recrystallized from ethanol. Yield of desired 1-propanone, 1-cyclohexyl-3-((2-hydroxy-1-methyl-2- phenylethyl)amino)-, (R-(R*,S*) hydrochloride 24%, M.P: 219-221°C.
2). 13.8 g (0.1 mol) of cyclohexylvinyl ketone (obtainable by the splitting off of HCl during the distillation of cyclohexyl-β-chloroethyl ketone) and 15.1 g (0.1 mol) of 1-norephedrine were dissolved in 50 ml of isopropanol. The desired compound crystallized out as the free base in the standing overnight. The hydrochloride was made with isopropanolic hydrochloric acid. M.P. of the hydrochloride: 219-221°C.
3). The oily cyclohexyl-β-chloroethyl ketone obtained from a solution of 200 g (1.36 mol) of cyclohexanecarboxylic acid chloride in 500 ml of dried 1,2- dichloroethane by portion-wise addition of 182 g (1.3 mol) of AlCl3 at -5°C, then leading ethylene through, subsequent hydrolysis with 500 ml of water at room temperature and concentration of the organic phase dried with Na2SO4 in a vacuum (analogous to U.S. Pat. No. 2,792,406) was added to a solution of 164 g (1.09 mol) of 1-norephedrine in 1000 ml of dioxane. The desired product crystallized out overnight, was filtered off with suction and recrystallized from ethanol/water 1:1 (by volume). Yield: 67% (based on the cyclohexane carboxylic acid chloride). M.P. of the hydrochloride: 219-221°C.

Sympathomimetic; Cardiotonic