α-[4-(Dimethylamino)cyclohexyl]-α-(2-thienyl)-2-thiophenemethanol

Sorboquel,Schering,US,1960

The requisite intermediate, ethyl 4-dimethylaminocyclohexylcarboxylate is prepared as follows: 33 g of ethyl p-aminobenzoate dissolved in 300 cc of absolute ethanol containing 16.8 cc of concentrated hydrochloric acid is hydrogenated at 50 pounds hydrogen pressure in the presence of 2 g of platinum oxide. The theoretical quantity of hydrogen is absorbed in several hours, the catalyst removed by filtration and the filtrate concentrated to dryness in vacuo. The residue is dissolved in water, made alkaline with ammonium hydroxide and extracted with chloroform. After removal of the solvent, the residual oil is distilled to yield ethyl 4- aminocyclohexylcarboxylate, boiling point 114°C to 117°C/10 mm.
A mixture of 49 g of this ester compound, 76 g of 98% formic acid and 68 ml of formalin solution is heated under reflux for 8 hours. The solvents are then removed in vacuo on the steam bath, the residue dissolved in water, made alkaline with ammonium hydroxide and extracted with chloroform. Removal of the solvent and distillation in vacuo yields ethyl 4- dimethylaminocyclohexylcarboxylate, boiling point 122°C to 125°C/10 mm.
To a solution of thienyl magnesium bromide prepared from 21.4 g of magnesium and 144 g of 2-bromothiophene are added 39.8 g of ethyl 4- dimethylaminocyclohexylcarboxylate. The mixture is allowed to warm to room temperature and stirred for an additional six hours. The reaction mixture is then decomposed with dilute ammonium chloride solution and extracted with ether. The combined ether extracts are extracted thoroughly with 10% hydrochloric acid and the acid solution made alkaline with ammonium hydroxide. The aqueous solution is extracted with chloroform which is then washed with water, dried and evaporated to a residue in vacuo. Recrystallization of the residue from hexane yields α,α1-dithienyl-4- dimethylaminocyclohexyl carbinol, melting point 156°C to 157°C after recrystallization from benzene.

α-[4-(Diethylamino)cyclohexyl]-α-2-thienyl-2-thiophenemethanol