Condensation of 7-hydroxy-4,8-dimethylcoumarin (I) with 3-chloro-2-butanone (II) affords the keto alkoxycoumarin (III), which is cyclized to the psoralen derivative (IV) under basic conditions. Benzylic bromination of (IV) by means of N-bromosuccinimide provides the bromomethyl compound (V) as the major isomer. Bromide (V) is then condensed with N-(2-hydroxyethyl)phthalimide (VI) to furnish ether (VII). The phthaloyl group of (VII) is removed by treatment with either primary amines or with hydrazine to produce the target free amine, which is finally isolated as the corresponding hydrochloride salt.
A different method starts with the chloromethylation of trimethyl psoralen (I) to afford (II). Subsequent condensation of chloride (II) with ethylene glycol (III) yields the hydroxyethoxy derivative (IV). This is converted to mesylate (V) upon treatment with methanesulfonyl chloride and triethylamine. Mesylate displacement by NaN3 leads to azide (VI). Finally, azide reduction to the target amine is accomplished by treatment with triphenylphosphine in moist THF.