反应详情

温度

-70 °C

A mixture of magnesium metal (4.81 g, 200 mmol) and dry tetrahydrofuran (10 mL) under argon was treated with a solution of 1,2-dibromoethane (0.94 g, 5 mmol) in dry tetrahydrofuran (5 mL). The resulting reaction mixture was stirred for 10 min to activate the magnesium metal. The reaction mixture was then treated dropwise with a solution of cycloheptyl bromide (17.7 g, 100 mmol) in dry tetrahydrofuran (30 mL), one-fifth portion over a period of 5 min. The resulting reaction mixture was stirred for 5–10 min to initiate the exothermic reaction. The remaining portion of the cycloheptyl bromide solution was then added dropwise while controlling the inside temperature below 50° C. After complete addition, the solution was stirred for 1 h and then diluted with dry tetrahydrofuran (80 mL). In a separate reaction flask, a mixture of lithium chloride (8.48 g, 200 mmol, predried at 130° C. under high vacuum for 3 h) and copper(I) cyanide (8.96 g, 100 mmol) in dry tetrahydrofuran (110 mL) was stirred at 25° C. under argon for 10 min to obtain a clear solution. The reaction mixture was cooled to −70° C. and then slowly treated with the freshly prepared cycloheptylmagnesium bromide. After the addition, the reaction mixture was allowed to warm to −10° C. where it was stirred for 5 min. The resulting reaction mixture was again cooled back to −70° C. and then treated with methyl propiolate (7.57 g, 90 mmol). The reaction mixture was stirred for 15 h at −70° C. to −50° C. and then slowly treated with a solution of iodine (34.3 g, 135 mmol) in dry tetrahydrofuran (30 mL) while maintaining the temperature at −70° C. to −60° C. After addition of the iodine solution, the cooling bath was removed, and the reaction mixture was allowed to warm to 25° C. where it was stirred for 2 h. The reaction mixture was then poured into a solution consisting of a saturated aqueous ammonium chloride solution (400 mL) and ammonium hydroxide (100 mL), and the organic compound was extracted into ethyl acetate (3×200 mL). The combined organic extracts were successively washed with a saturated aqueous sodium thiosulfate solution (1×400 mL) and a saturated aqueous sodium chloride solution (1×400 mL). The organic layer was then dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230–400 mesh, 20/1 to 10/1 hexanes/diethyl ether) afforded (E)-3-cycloheptyl-2-iodo-acrylic acid methyl ester (17.86 g, 64%) as a colorless oil: EI-HRMS m/e calcd for C11H17IO2 (M+) 308.0273, found 308.0273.

1. customThe resulting reaction mixture
2. customThe resulting reaction mixture
3. stirringwas stirred for 5–10 min
4. customthe exothermic reaction
5. customthe inside temperature below 50° C
6. additionAfter complete addition
7. stirringthe solution was stirred for 1 h
8. customIn a separate reaction flask
9. stirringwas stirred at 25° C. under argon for 10 min
10. customto obtain a clear solution
11. additionAfter the addition
12. temperatureto warm to −10° C. where it
13. stirringwas stirred for 5 min
14. customThe resulting reaction mixture
15. temperaturewas again cooled back to −70° C.
16. stirringThe reaction mixture was stirred for 15 h at −70° C. to −50° C.
17. temperaturewhile maintaining the temperature at −70° C. to −60° C
18. customthe cooling bath was removed
19. temperatureto warm to 25° C. where it
20. stirringwas stirred for 2 h
21. additionThe reaction mixture was then poured into a solution
22. extractionthe organic compound was extracted into ethyl acetate (3×200 mL)
23. washThe combined organic extracts were successively washed with a saturated aqueous sodium thiosulfate solution (1×400 mL)
24. dry with materialThe organic layer was then dried over anhydrous magnesium sulfate
25. filtrationfiltered
26. concentrationconcentrated in vacuo