Iodine → (E)-3-cycloheptyl-2-iodo-acrylic acid methyl ester

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 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), with the temperature kept 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-IIRMS 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. customkept 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

ORDレコード

ord-c2d366eb401742cab9ce98b0eda8da0e

出典データセット

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06353111B1