Benzylamine → Methyl 2-benzylisoindoline-5-carboxylate

Participants

Reaction Steps

The [2-(aminocarbonyl)-2,3-dihydro-1H-isoindol-5-yl]methanamine of general formula III may be prepared as follows, for example: The methyl 3,4-bis-(bromomethyl)benzoate obtainable in situ from methyl 3,4-dimethylbenzoate by photobromination, on being reacted with benzylamine, yields methyl 2,3-dihydro-2-(phenyl-methyl)-1H-isoindol-5-carboxylate, the ester function of which is converted in the usual way into a carboxamide function and then, by reduction with lithium aluminium hydride, into an aminomethyl function; the primary amino group is protected with a tert.butoxycarbonyl group, the benzyl group in the 2-position is removed by hydrogenolysis and replaced by an aminocarbonyl group, e.g. by treating the hydrochloride of the resulting 5-[[(tert.butoxycarbonyl)amino]methyl]-2,3-dihydro-1H-isoindole with sodium cyanate; removal of the tert.butoxycarbonyl protecting group, e.g. with methanolic hydrogen chloride solution, then yields the desired 2-(amino-carbonyl)-2,3-dihydro-1H-isoindol-5-yl]methanamine in the form of the hydrochloride.

Provenance & Evidence