反应详情

To a solution (1500 ml) of ethyl 1-acetylcyclopropanecarboxylate (124.5 g, 0.797 mmol) in benzene was added zinc powder (156.4 g, 2.39 mmol). While heating under reflux, a catalytic amount of iodine was added thereto. Subsequently, a solution of ethyl bromofluoroacetate (94.23 ml, 0.797 mol) in benzene (200 ml) was added dropwise thereinto over a period of 1 hour followed by heating under reflux for 1 hour. Under ice cooling, 1 N hydrochloric acid (1000 ml) was added to the liquid reaction mixture and the mixture was stirred for 1 hour. The organic layer taken up by phase separation was washed successively with 1 N hydrochloric acid, water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in pyridine (387 ml, 4.78 mol). After adding thionyl chloride (69.8 ml, 0.957 mol) at −10° C., the resultant mixture was stirred under ice cooling for 3 hours. Under ice cooling, the liquid reaction mixture was poured into 1 N hydrochloric acid (2000 ml) and ethyl acetate (1500 ml) was added thereto. The organic layer taken up by phase separation was washed successively with 1 N hydrochloric acid, water and a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in dichloromethane (500 ml). Under ice cooling, 1,8-azabicyclo[5.4.0]-7-undecene (131 ml, 0.877 mol) was added dropwise thereinto and then the resultant mixture was stirred at room temperature for 17 hours. After adding 1 N hydrochloric acid (2000 ml) and chloroform (1000 ml), the organic layer taken up by phase separation was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the residue thus obtained was subjected to flash silica gel column chromatography (eluent: n-hexane:ethyl acetate=4:1) 152.78 g (78.5%) of the title compound as an oily substance. The compound thus obtained, which was a mixture of geometrical isomers (about 1:1), was not separated but employed in the subsequent reaction as such.

1. temperatureWhile heating
2. temperatureunder reflux
3. temperatureby heating
4. temperatureunder reflux for 1 hour
5. customThe organic layer taken up by phase separation
6. washwas washed successively with 1 N hydrochloric acid, water
7. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationThe filtrate was concentrated under reduced pressure
10. customUnder ice cooling, the liquid reaction mixture
11. additionwas added
12. customThe organic layer taken up by phase separation
13. washwas washed successively with 1 N hydrochloric acid, water
14. dry with materiala saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate
15. filtrationfiltered
16. concentrationThe filtrate was concentrated under reduced pressure
17. dissolutionthe residue was dissolved in dichloromethane (500 ml)
18. customthe organic layer taken up by phase separation
19. washwas washed with a saturated aqueous solution of sodium chloride
20. dry with materialdried over anhydrous sodium sulfate
21. filtrationfiltered
22. concentrationThe filtrate was concentrated under reduced pressure
23. customthe residue thus obtained