反应详情

A mixture of N-(3-tert-butoxycarbonyl-thien-2-yl)-methylaminomethylenemalonic acid diethyl ester (19.0 g) from Preparation No. 2 and 4-methylene morpholinium chloride (Dimmock, JR, et al Eur. J. Med. Chem. 1989, 24, 379-383) (13.4 g) in dry acetonitrile (50 ml) is heated at reflux for about 4 hr. The solution is then cooled in an ice bath and saturated aqueous sodium carbonate (98 ml) is slowly added. The solution is extracted three times with ethyl acetate (300 ml total) and the combined organic layers are then washed three times with water (600 ml total). The solvents are removed in vacuo to afford 23.0 g (96%) of the title compound as a brown oil.

1. customfrom Preparation No
2. temperatureat reflux for about 4 hr
3. temperatureThe solution is then cooled in an ice bath
4. extractionThe solution is extracted three times with ethyl acetate (300 ml total)
5. washthe combined organic layers are then washed three times with water (600 ml total)
6. customThe solvents are removed in vacuo