反应详情

温度

-78 °C

Under a nitrogen atmosphere, chloromethyltrimethyl-phosphonium chloride (5.156 g, 14.85 mmol) was suspended in dry tetrahydrofuran (30 ml). After cooling the suspension to provide an internal temperature of -55° C., a 1.68 M solution of n-butyllithium in n-hexane (8.87 ml, 14.90 mmol) was added dropwise thereinto over a period of 5 minutes. Then, the reaction suspension was stirred under ice cooling for 30 minutes and then at room temperature for an additional 3 hours followed by cooling to provide an internal temperature of -55° C. Into this reaction suspension was added dropwise a solution of 1-tert-butoxycarbonylaminocyclopropane carbaldehyde (2.49 g, 13.50mmol) in dry tetrahydrofuran (10 ml) over a period of 10 minutes and the resultant mixture was stirred at -50° C. for 1 hour and then under ice cooling for additional 30 minutes. The reaction suspension was cooled to -78° C. and a 1.68 M solution of n-butyllithium in n-hexane (17.68 ml, 29.70 mmol) was added dropwise thereinto over a period of 10 minutes followed by stirring at -78° C. for 20 minutes. Next, ethyl chloroformate (1.61 ml, 16.88 mmol) was added dropwise into this reaction suspension followed by stirring at -78° C. for 1.5 hours and then under ice cooling for 1 hour. Under ice cooling, a saturated aqueous solution of sodium chloride (30 ml) was added to the reaction suspension and the organic layer was separated. The aqueous layer was extracted with diethyl ether (30 ml×2) and the combined organic layer was washed with a saturated aqueous solution of sodium chloride (30 ml) and dried over anhydrous magnesium sulfate. After filtering, the filtrate was concentrated under reduced pressure and the residue was subjected to flash silica gel column chromatography (eluent: n-hexane:ethyl acetate=5:1) to obtain 2.178 g (63.9%) of the title compound as a colorless oily substance.

1. temperatureAfter cooling the suspension
2. customto provide an internal temperature of -55° C.
3. waitat room temperature for an additional 3 hours followed
4. temperatureby cooling
5. customto provide an internal temperature of -55° C
6. waitunder ice cooling for additional 30 minutes
7. waitover a period of 10 minutes followed
8. stirringby stirring at -78° C. for 20 minutes
9. stirringby stirring at -78° C. for 1.5 hours
10. waitunder ice cooling for 1 hour
11. customthe organic layer was separated
12. extractionThe aqueous layer was extracted with diethyl ether (30 ml×2)
13. washthe combined organic layer was washed with a saturated aqueous solution of sodium chloride (30 ml)
14. dry with materialdried over anhydrous magnesium sulfate
15. filtrationAfter filtering
16. concentrationthe filtrate was concentrated under reduced pressure