反应详情

温度

-12 °C

(i)(b) 45.4 g (180 mmol) of N-benzyloxycarbonyl-L-norvaline were stirred in 200 ml of methylene chloride while 31.76 g (180 mmol) of dimethyl aminomethylphosphonate hydrochloride were added. The resulting suspension was cooled to -12° C. and 25.3 ml (180 mmol) of dry triethylamine were added dropwise. After completion of the addition, the cold mixture was stirred for 0.25 hour. 56.8 g (230 mmol) of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline in 100 ml of methylene chloride were then added rapidly. The mixture was stirred in the cold for 2 hours and then at room temperature overnight. The mixture was washed with 100 ml of water and then with four 100 ml portions of 1-N hydrochloric acid. The combined acid washings were back-extracted with two 50 ml portions of methylene chloride. The combined organic solutions were washed with 100 ml of water and finally with three 100 ml portions of 15% potassium bicarbonate solution, then dried over anhydrous sodium sulphate, filtered and evaporated. The residual oil was re-evaporated with benzene to give an oil which was triturated with 200 ml of anhydrous ether. There were obtained 58.2 g of crude product of melting point 77°-80° C. Recrystallization from 200 ml of ethyl acetate gave 50.6 g of dimethyl N-benzyloxycarbonyl-L-norvalyl-aminomethylphosphonate of melting point 82°-84° C.

1. additionwere added
2. additionAfter completion of the addition
3. stirringThe mixture was stirred in the cold for 2 hours
4. customat room temperature
5. customovernight
6. washThe mixture was washed with 100 ml of water
7. extractionThe combined acid washings were back-extracted with two 50 ml portions of methylene chloride
8. washThe combined organic solutions were washed with 100 ml of water and finally with three 100 ml portions of 15% potassium bicarbonate solution
9. dry with materialdried over anhydrous sodium sulphate
10. filtrationfiltered
11. customevaporated
12. customThe residual oil was re-evaporated with benzene
13. customto give an oil which
14. customwas triturated with 200 ml of anhydrous ether
15. customThere were obtained 58.2 g of crude product of melting point 77°-80° C
16. customRecrystallization from 200 ml of ethyl acetate