反应详情

Triethylamine (0.48 ml) is added to a mixture of (-)-(isochroman-1-yl)acetic acid (LXI, EXAMPLE 45 Step 3, 0.2016 g, 1.05 mmol), DMF (1.1 ml), dichloromethane (1.1 ml), 1-(4-ethoxyphenyl)piperazine dihydrochloride (XXIV, 0.2997 g, 1.07 mmol) and diethyl cyanophosphonate (0.21 ml). After 2 hr, saturated sodium bicarbonate is added and the mixture is stirred for 2 hr and then extracted several times with dichloromethane. The combined organic phases are backwashed with saline, dried over magnesium sulfate, concentrated, and the residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give a residue which upon crystallization from ethyl acetate/hexane gives 2-(isochroman-1-yl)-1-[4-(4-ethoxyphenyl)piperazin-1-yl]-2-methylpropan-1-one (LXXXII), MS (m/z) 380; IR (mineral oil) 1620, 1248, 1515, 1107, 1444 and 815 cm-1.

1. extractionextracted several times with dichloromethane
2. dry with materialdried over magnesium sulfate
3. concentrationconcentrated
4. customthe residue chromatographed on silica gel eluting with methanol/dichloromethane (2/98)
5. concentrationconcentrated
6. customto give a residue which
7. customupon crystallization from ethyl acetate/hexane