反应详情

A solution of ethyl chloroformate (20.4 g, 0.19 mol) in acetic acid (150 ml) is added dropwise with stirring to a solution of 2-(2-thienyl)-piperazine (31.6 g, 0.19 mol; Preparation 1) in acetic acid (150 ml) at 65° C. under an atmosphere of dry nitrogen. After 1 h, the solution is allowed to cool to room temperature, and stirring is maintained for an additional 16 h. The reaction mixture is added to chilled 10N NaOH (750 ml) and ice is added to control the exothermic reaction. The mixture is extracted with methylene chloride (4×300 ml), the organic solution is dried(potassium carbonate), and the solvent removed under reduced pressure to give the carbamate (30.0 g) as a light brown oil. This material is dissolved in methanol (250 ml), and the solution added to a solution of maleic acid (18.6 g; 1 eq) in methanol (250 ml). The mixture is treated with charcoal and the solvent removed under reduced pressure to give an oil which crystallizes on trituration with ethyl acetate. The maleate salt melts at 165°-166° C.

1. temperatureis maintained for an additional 16 h
2. additionThe reaction mixture is added
3. additionis added
4. customthe exothermic reaction
5. extractionThe mixture is extracted with methylene chloride (4×300 ml)
6. customthe solvent removed under reduced pressure