[Synthesis]
The general procedure for the synthesis of tetrahydrofuran-2-carboxamidine hydrochloride from methyl tetrahydrofuran-2-carboxylate was as follows: 41.1 g (768 mmol, 5 eq.) of ammonium chloride was suspended in 400 ml of anhydrous toluene under argon protection and the mixture was cooled to 0 °C. 385 ml (768 mmol, 5 eq.) of a hexane solution of 2M trimethylaluminum was slowly added dropwise, followed by stirring the reaction mixture at room temperature until no gas was released. After addition of 20 g (154 mmol, 1 eq.) of methyl tetrahydrofuran-2-carboxylate, the mixture was stirred in an oil bath at 80 °C overnight. Upon completion of the reaction, the mixture was cooled to 0 °C and 200 ml of methanol was slowly added while stirring was continued for 1 h at room temperature. After filtration, the solid was washed several times with methanol, the filtrate was combined and concentrated to dryness in vacuum. Finally 15.9 g (69% yield) of the target product tetrahydrofuran-2-carboxamidine hydrochloride was obtained. |