Iodine → (E)-4-cyclopentyl-2-iodo-but-2-enoic acid methyl ester

온도

25 °C

A mixture of zinc dust (3.92 g, 60 mmol, Aldrich, −325 mesh) and dry tetrahydrofuran (4 mL) under argon was treated with 1,2-dibromoethane (0.56 g, 3 mmol). The zinc suspension was then heated with a heat gun to ebullition, allowed to cool, and heated again. This process was repeated three times to make sure the zinc dust was activated. The activated zinc dust suspension was then treated with trimethylsilyl chloride (0.32 g, 3 mmol, and the suspension was stirred for 15 min at 25° C. The reaction mixture was then treated dropwise with a solution of cyclopentylmethyl iodide (4.2 g, 20 mmol) in dry tetrahydrofuran (7 mL) over 5 min. During the addition, the temperature rose to 50° C., and the reaction mixture was stirred overnight at 40-45° C. The reaction mixture was then cooled to 25° C. and diluted with dry tetrahydrofuran (5 mL). The stirring was stopped to allow the excess zinc dust to settle down (˜2 h). In a separate reaction flask, a mixture of lithium chloride (1.7 g, 40 mmol, predried at 130° C. under high vacuum for 2 h) and copper cyanide (1.79 g, 20 mmol) in dry tetrahydrofuran (20 mL) was stirred for 10 min at 25° C. to obtain a clear solution. The reaction mixture was cooled to −70° C. and then the slowly treated with the freshly prepared zinc solution using a syringe. After the addition, the reaction mixture was allowed to warm to −30° C., where it was stirred for 5 min. The reaction mixture was again cooled back to −70° C. and then slowly treated with methyl propiolate (1.52 g, 18 mmol). The reaction mixture was stirred for 4 h at −40° C. to −30° C. and then slowly treated with a solution of iodine (6.85 g, 27 mmol) in dry tetrahydrofuran (10 mL), with the temperature kept at −70° C. to −60° C. After the 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 1 h. The reaction mixture was then poured into a solution consisting of a saturated aqueous ammonium chloride solution (90 mL) and anunonium hydroxide (10 mL), and the organic compound was extracted into diethyl ether (3×50 mL). The combined ether extracts were successively washed with a saturated aqueous sodium thiosulfate solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtrated, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 9/1 hexanes/diethyl ether) afforded (E)-4-cyclopentyl-2-iodo-but-2-enoic acid methyl ester (4.56 g, 86%) as a colorless oil: EI-HRMS m/e calcd for C10H15IO2 (M+) 294.0116, found 294.0114.

1. temperatureto cool
2. temperatureheated again
3. additionDuring the addition
4. customrose to 50° C.
5. stirringthe reaction mixture was stirred overnight at 40-45° C
6. temperatureThe reaction mixture was then cooled to 25° C.
7. custom(˜2 h)
8. customIn a separate reaction flask
9. stirringwas stirred for 10 min at 25° C.
10. customto obtain a clear solution
11. temperatureThe reaction mixture was cooled to −70° C.
12. additionAfter the addition
13. temperatureto warm to −30° C.
14. stirringwhere it was stirred for 5 min
15. temperatureThe reaction mixture was again cooled back to −70° C.
16. stirringThe reaction mixture was stirred for 4 h at −40° C. to −30° 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 1 h
21. additionThe reaction mixture was then poured into a solution
22. extractionthe organic compound was extracted into diethyl ether (3×50 mL)
23. washThe combined ether extracts were successively washed with a saturated aqueous sodium thiosulfate solution (1×100 mL)
24. dry with materiala saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate
25. filtrationfiltrated
26. concentrationconcentrated in vacuo

ORD 기록

ord-3963a1034160427083e4f844ec0e14b5

출처 데이터셋

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06388088B1