Dimethylamine → Dapoxetine

Participants

Reaction Conditions

Reaction Steps

50 gms of 1-phenyl,3-napthyloxy 1-propanol, 375 ml of tetrahydrofuran (THF)), 5 mg of dimethylamino pyridine (DMAP) and 60 ml of triethyl amine) were charged in a clean and dry R.B. flask. The reaction mixture was cooled to −5 to 0° C. and a mixture of methane sulfonyl chloride (33 gm) and tetrahydrofuran (125 ml) was added. The resultant reaction mixture was stirred at about 0 to 5° C. for 6 hours and then dimethylamine gas was passed into the reaction mass. The temperature of the reaction mass was raised to room temperature and stirred for about 40 hours. After the completion of the reaction as determined by TLC, the reaction mass was quenched by pouring into chilled water (500 ml) slowly and the pH was adjusted to 0.5 to 1 with concentrated hydrochloric acid. 250 ml of toluene (250 ml) was added and stirred for 30 minutes. The layers were separated and the aqueous layer pH was adjusted to 9 to 10 with 5% w/v sodium hydroxide solution. The aqueous layer extracted with methylene dichloride (4×300 ml) and the solvent distilled off completely to obtain a residue. 100 ml of Ethyl acetate was added to the residue obtained and the mixture was stirred for about 30 minutes, filtered through celite and washed with ethyl acetate. The filtrate was distilled off completely to obtain 47 gm of racemic dapoxetine as a residual oil.

Provenance & Evidence