反应详情

Diethylphosphonoacetic acid (32.8 g, 166 mmol) was dissolved in anhydrous benzene (700 ml), and after adding N,N′-dimethylformamide (1 ml, thionyl chloride (18.2 ml, 250 mmol) was added thereto and heated under reflux for 1.5 hours. After letting the reaction solution cool, it was concentrated under a reduced pressure, and after adding dried toluene (100 ml) thereto, its concentration under a reduced pressure was performed again. After repeating this operation 3 times, the concentrate was dissolved in anhydrous tetrahydrofuran (300 ml) and after adding dropwise an anhydrous tetrahydrofuran (300 ml) solution of ethyl 1-[2-[N-[1-(S)-phenylethyl]amino]acetyl]cyclopropanecarboxylate (45.7 g, 166 mmol) and triethylamine (25.1 ml, 183 mmol) while stirring and cooling with ice, it was stirred while cooling with ice for 1.5 hours and then stirred at room temperature for 2 hours. After adding 1 mol/l hydrochloric acid (300 ml) and ethyl acetate (300 ml) to the reaction solution and performing an extraction operation, the organic layer was separated. The aqueous layer was then subjected to extraction with ethyl acetate (300 ml) and the combined organic layer was washed with saturated sodium bicarbonate water (300 ml) and saturated saline solution (300 ml) in that order, and then dried over anhydrous sodium sulfate. After filtering and then concentrating the filtrate under a reduced pressure, 43.6 g (70%) of the title compound was obtained as a yellow syrup.

1. additionwas added
2. temperatureheated
3. temperatureunder reflux for 1.5 hours
4. temperaturecool
5. concentrationit was concentrated under a reduced pressure
6. additionafter adding dried toluene (100 ml)
7. concentrationits concentration under a reduced pressure
8. dissolutionthe concentrate was dissolved in anhydrous tetrahydrofuran (300 ml)
9. temperaturecooling with ice, it
10. stirringwas stirred
11. temperaturewhile cooling with ice for 1.5 hours
12. stirringstirred at room temperature for 2 hours
13. customthe organic layer was separated
14. extractionThe aqueous layer was then subjected to extraction with ethyl acetate (300 ml)
15. washthe combined organic layer was washed with saturated sodium bicarbonate water (300 ml) and saturated saline solution (300 ml) in that order
16. dry with materialdried over anhydrous sodium sulfate
17. filtrationAfter filtering
18. concentrationconcentrating the filtrate under a reduced pressure