Hydrochloric Acid → (+/-)-Methyl 4-benzyl-1-methylpiperidine-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 480 mg of Mg in 2 mL of dry ether was added a little bit of I2 and several drops of benzyl chloride (about 0.5 mL) of the solution of 2.3 mL (20 mmol) of benzyl chloride in 10 mL of ether. The mixture was gentle stirred, as soon as the reaction sets in, the reminder of benzyl chloride in ether was added at the rate that the reaction went vigorously by cooling the flask with water. Then the resulting solution was stirred at gentle reflux for fifteen minutes after all the benzyl chloride has been added. Another 5 mL of dry ether was added to the Grignard reagent solution and it was cooled to −15° C., the arecoline (1.5 g) in 20 mL of dry ether was added dropwise to it. The resulting mixture was stirred at −15° C. for another 0.5 hour. The mixture was cooled to about −40° C. and treated slowly with 10% HCl (22 mL). The aqueous layer was separated, extracted with ether (20 mL), and then basified with saturated sodium bicarbonate solution when cooled in an ice bath. The mixture was extracted with ether and the combined organic extracts were washed with brine, dried and concentrated under reduced pressure. Flash chromatography afforded a mixture of cis isomer 76 and trans isomer 77 (500 mg, 21%).

Provenance & Evidence