Tetrahydrofuran → HCID 12917752, compound

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Reaction Steps

A solution of (±)-ethyl 2-amino-4,5,6,7-tetrahydro-6-benzothiazolecarboxylate (13.5 g) (Example C) in 700 ml of anhydrous tetrahydrofuran is cooled in an ice bath and lithium aluminum hydride (4.56 g) is added in small portions. A thick suspension forms which is kept at room temperature for one hour. The reaction mixture is quenched by careful addition of a 10% solution of hydrochloric acid. The volatile components are evaporated in vacuo and the residue is stirred with a 25% solution of sodium hydroxide and dichloromethane for 30 minutes. An emulsion forms which is filtered through Celite. The aqueous phase is extracted with dichloromethane several times. The pooled organic extracts are dried and evaporated. The residue is recrystallized from ethyl acetate to give (±)-4,5,6,7-tetrahydro-6-benzothiazolemethanol as a colorless solid, mp 176°-182° C. A solution of this compound (5.0 g) in 500 ml of chloroform is treated with 25 ml of a 1 M hydrochloric acid-diethyl ether solution, followed by 50 ml of thionyl chloride. The reaction mixture is refluxed under nitrogen for one hour until evolution of gas ceases. The mixture is concentrated in vacuo and the residue is taken up into 100 ml of dimethylformamide. To this solution is added 1-(2-pyridyl)piperazine (4.89 g) and sodium bicarbonate (5.0 g) and the mixture is heated at 85° C. for six hours. The solvent is evaporated in vacuo, and the residue is partitioned between dichloromethane and water. The organic layer is dried (magnesium sulfate) and purified by MPLC. The hydrochloride salt is prepared to give (±)-4,5,6,7-tetrahydro-6-[[4-(2-pyridinyl)-1-piperazinyl]methyl]benzothiazole containing 2.85 molecules of hydrochloric acid and 1.1 molecules of water; mp 251°-252° C.

Provenance & Evidence