Hexamethylenetetramine → Ethyl 2-aminomethyl-6-methoxyisonicotinate

Participants

Reaction Steps

6.72 g (47.9 mmol) of hexamethylenetetramine (urotropin) were initially introduced in 250 ml of chloroform and a solution of 10.95 g (39.95 mmol) of ethyl 2-bromomethyl-6-methoxyisonicotinate (20c) in chloroform was added dropwise at 0° C. The mixture was stirred at RT for 4.5 hours and after this a further 3.36 g (24.0 mmol) of hexamethylenetetramine (urotropin) was added. After standing at RT for a further 60 hours, the solvent was distilled off under reduced pressure and the residue was dissolved in 500 ml of ethanol. 50 ml of concentrated HCl were added and the mixture was stirred at RT for two hours. After addition of a further 30 ml of concentrated HCl and stirring at RT overnight, it was freed from the solvent under reduced pressure. The residue was taken up in DCM and carefully treated with K2CO3 until evolution of gas was no longer observed. Subsequently, it was washed twice with saturated K2CO3 solution, and the organic phase was dried with MgSO4 and concentrated. The crude product thus obtained (7.60 g) was reacted further without further purification. LCMS-Rt: 0.74 min [M+H+]: 211.2

Provenance & Evidence