Thiophenol → Desmetramadol

Participants

Reaction Steps

First, O-desmethyl tramadol was prepared as set forth hereinafter. Diethylene glycol (125 mL) was added with cooling to potassium hydride (9.5 g) with the temperature being maintained at <50° C. To the solution was added thiophenol (10 mL) dissolved in diethylene glycol (25 mL), and then (-)-tramadol as the free base (9.3 g) in diethylene glycol (50 mL) was added. The final reaction mixture was heated slowly to reflux for 45 minutes. The mixture was cooled and quenched with water. The pH was adjusted to about 3, and the mixture was extracted with ethyl ether. The pH was readjusted to about 8 and the resulting mixture was extracted 5 more times with methylene chloride. The extract was dried and the methylene chloride was evaporated to yield 4.6 g of the title compound. The title compound (4.6 g) was distilled (Kugelrohr), was dissolved in tetrahydrofuran and treated with an ethanol/HCl solution to give 2.3 g of the hydrochloride salt. The salt was recrystallized from ethanol/ethyl ether and dried to yield 1.80 g of the salt of the (-) enantiomer of O-desmethylated tramadol (mp. 242°-3° C.), [α]D25 =-32.9 (C=1, EtOH).

Provenance & Evidence