反应详情

温度

90 °C

To 1.88 g N-carbobenzyloxy-γ-tert.butyl-L-glutamic acid-dicyclohexyl ammonium salt, 24 ml ethyl acetate and 3.3 ml solution of dimethylaminoethylchloride in the amount of 0.78 g, stoichiometrically corresponds to two times the molar volume, in benzene were added to be subjected to reflux in oil bath at 90° C. for 16 hrs. After cooling down to a room temperature, precipitated dicyclohexyl ammonium chloride was filtered off and ethyl acetate phase in the filtrate was washed with diluted hydrochloride to remove excessive dimethylaminoethylchloride contained therein. The filtrate was further washed with 10% aqueous solution of hydrogen sodium bicarbonate so as to remove unreacted starting meterial, N-carbobenzyloxy-γ-tert.butyl-L-glutamic acid-dicyclohexyl-ammonium salt and then with saturated brine to be neutral, which was then treated with sulfuric sodium anhydride for dehydration and subjected to reduced pressure distillation so as to distill off ethyl acetate and obtain Intermediate I, N-carbobenzyloxy-γ-tert.butyl-L-glutamic acid-dimethylamino-ethyl ester in the amount of 1.43 g (yield; 96.6% by weight).

1. temperatureAfter cooling down to a room temperature
2. customprecipitated dicyclohexyl ammonium chloride
3. filtrationwas filtered off
4. washethyl acetate phase in the filtrate was washed with diluted hydrochloride
5. customto remove excessive dimethylaminoethylchloride
6. washThe filtrate was further washed with 10% aqueous solution of hydrogen sodium bicarbonate so as
7. customto remove unreacted
8. additionwhich was then treated with sulfuric sodium anhydride for dehydration
9. distillationsubjected to reduced pressure distillation so as
10. distillationto distill off ethyl acetate