Diisopropylethylamine → 1-[2-(Isochroman-1-yl)ethyl]-4-(2-methylphenyl)piperazine dihydrochloride

Participants

Reaction Steps

A mixture of 1-(2-chloroethyl)isochroman (LXIV, PREPARATION 2, 0.2466 g, 1.25 mmol), 1-(2-methylphenyl)piperazine dihydrochloride (XI, 0.5327 g, 2.14 mmol), diisopropylethylamine (0.98 ml, 5.63 mmol) and ethylene glycol (2.5 ml) is stirred under nitrogen at 100° for 3 days. The reaction mixture is cooled and partitioned between aqueous sodium bicarbonate and ethyl acetate. The combined organic phase is washed with saline, dried over magnesium sulfate and concentrated. The residue is chromatographed on silica gel eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give the free base of the title compound. The dihydrochloride salt is formed using hydrochloric acid/methanol to give the title compound, mp 207.5-210.5°; MS (m/z) 336; IR (mineral oil) 770, 2406, 2435, 2992, 2364 and 1489 cm-1.

Provenance & Evidence