反应详情

A solution of 1-(1,4-benzodioxan-6-yl)piperazine prepared as described in Example 1 (0.146 g, 0.663 mmol) in CH3CN (5 mL) is treated with potassium carbonate (0.458 g, 3.32 mmol) and 4-fluorobenzyl chloride (0.144 g, 0.995 mmol). The mixture is heated at reflux for 4 hours. The resulting mixture is then cooled to room temperature and washed successively with saturated aqueous NH4Cl (20 mL) and saturated aqueous NaCl (20 mL). The organic portion is dried over Mg2SO4, filtered and concentrated. Purification by flash column chromatography (30% ethyl acetate-hexane) gives 0.074 g (34%) of 1-(1,4 benzodioxan-6-yl)-4-(4-fluorobenzyl) piperazine as a white solid (TLC Rf 0.35; 30% ethyl acetate:hexane). A solution of this material in 1 mL of ethanol is treated with oxalic acid (0.020 g, 0.225 mmol) and concentrated to give 1-(1-(1,4-benzodioxan-6-yl)-4-(4-fluorobenzyl) piperazine oxalic acid salt (Compound 1) 0.079 g (88%), m.p. 177-179° C.

1. temperatureThe mixture is heated
2. temperatureat reflux for 4 hours
3. washwashed successively with saturated aqueous NH4Cl (20 mL) and saturated aqueous NaCl (20 mL)
4. dry with materialThe organic portion is dried over Mg2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification by flash column chromatography (30% ethyl acetate-hexane)