[Synthesis]
Tetrahydrofurfuryl alcohol (2.01 g, 19.7 mmol, 1.0 eq.) was dissolved in dichloromethane (100 mL) under argon protection and cooled to 0 °C. Triethylamine (3.02 mL, 21.7 mmol, 1.1 eq.) and methanesulfonyl chloride (1.60 mL, 20.7 mmol, 1.05 eq.) were added sequentially. The ice bath was removed and the reaction mixture continued to stir for 14 hours. Subsequently, the mixture was transferred to a partition funnel and water was added for phase separation. The organic phase was washed with water (4 times), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford the crude tetrahydrofurfuryl methanesulfonate (3.26 g, 92% yield) as a light yellow oil, which was used directly in the next step of the reaction.
The above crude tetrahydrofurfuryl methanesulfonate (1.0 g, 5.56 mmol, 1.0 eq.) was dissolved in DMSO (5 mL) under argon protection, and reacted with NaCN (817 mg, 16.7 mmol, 3 eq.) for 3.5 h at 80 °C. The reaction was completed by cooling to room temperature. After completion of the reaction, it was cooled to room temperature, diluted with ether and washed with saturated sodium bicarbonate solution. The aqueous phase was extracted with ether (4 times). The organic phases were combined, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure [note: the product may be volatile] to give the crude oil. Purification by fast column chromatography (20-50% ethyl acetate/hexane) gave the target product 2-(tetrahydrofuran-2-yl)acetonitrile (247 mg, 40% yield).
2-(Tetrahydrofuran-2-yl)acetonitrile (75 mg, 670 μmol, 1.0 equiv.) was reacted with BH3-THF solution (0.5 mL, 5 mmol, excess; 1.0 M in THF) under argon protection for 2 h at room temperature. The reaction solution was rotary evaporated to dryness to give a crude oil. It was carefully treated with the addition of methanol and rotary evaporated again. The residue was treated with methanol (0.5 mL) and 1.0 N aqueous hydrochloric acid (0.5 mL) overnight at room temperature and subsequently concentrated under reduced pressure. Purification by fast column chromatography (0-10% methanol/dichloromethane containing 1-2% ammonia) afforded the pure product 3-(tetrahydrofuran-2-yl)ethylamine (33 mg, 43% yield).ESI-MS (m/z) 116 [M + H]+. |