Hydrochloric Acid → 4,5,6,7-Tetrahydrothieno(3,2-c)pyridine

Participants

Reaction Conditions

Reaction Steps

Formaldehyde (37% in H2O, 3.82 g, 47 mmol) was added dropwise to a flask equipped with a magnetic stirring bar containing neat 2-(thiophen-2-yl)ethanamine (5 g, 39.3 mmol). The mixture was heated to 90° C. for 2 h and then allowed to cool down to room temperature. The reaction was then diluted with water and ethyl acetate. The organic layer was collected and dried with sodium sulfate, reduced in vacuo to give a thick oil. The thick oil was dissolved in anhydrous DMF (25 mL) and added dropwise to a DMF solution saturated with HCl gas (HCl gas was bubbled in DMF for 15 min at 10° C.). The reaction was stirred for 1 h and then poured unto crushed ice and rendered basic (pH 10) with 5 N NaOH. The mixture was extracted three times with dichloromethane. All the organic layers were combined, washed with a saturated aqueous solution of sodium bicarbonate, water and brine. The organic layer was then dried with sodium sulfate, reduced in vacuo and placed on a vacuum line to give a thick oil. Yield 5.47 g. MS (M+H)+ 140.

Provenance & Evidence