Methanesulfonic Acid → 1-(1-(3-Isothiocyanatophenyl)cyclohexyl)piperidine

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Reaction Steps

Metaphit was prepared as methanesulfonate and hydrochloride salts. To a vigorously stirred two-phase system consisting of 4.65 g (18 mmol) of m-amino-PCP (1-(1-(3-aminophenyl)cyclohexyl)piperidine) in 50 ml of chloroform and 756 mg (90 mmol) of sodium bicarbonate in 25 ml water, was added a solution of 1.45 ml (2.29 g, 19 mmol) of freshly distilled thiophosgene in 10 ml of chloroform. The mixture was stirred for 5 minutes, then the phases were separated and the aqueous phase was washed once with chloroform. The combined organic layers were dried (over sodium sulfate) and evaporated to a clear glass (5.43 g). This substance was dissolved in tetrahydrofuran (20 ml) and treated with a solution of methanesulfonic acid (1.73 g, 18 mmol) in tetrahydrofuran. The resulting crystalline solid was filtered and dried in vacuo to give 7.01 g (98%) of methanesulfonate salt, mp 175°-178° C. (dec). The material could be recrystallized from isopropanol/isopropyl ether if necessary. It was stored at 0° C. in a dessicator. The hydrochloride salt prepared in isopropanol and recrystallized from methanol-ether showed mp 214°-216 ° C. The methanesulfonate salt was considerably more soluble in water than the hydrochloride.

Provenance & Evidence