Iodine → HCID 86757834, compound

Temperature

25 °C

A mixture of lithium chloride (1.7 g, 40 mmol, predried at 130° C. under high vacuum for 2 h) and copper cyanide (1.78 g, 20 mmol) in dry tetrahydrofuran (20 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 a 1 M solution of ethylmagnesium bromide in tetrahydrofuran (20 mL, 20 mmol). After addition, the reaction mixture was allowed to warm to −30° C. where it was stirred for 5 min. The resulting 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 cooled to −70° C. to −60° C., at which time, the reaction mixture was treated slowly with a solution of iodine (6.86 g, 27 mmol) in dry tetrahydrofuran (20 mL). 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 1 h. The reaction mixture was then poured into a solution consisting of a saturated aqueous ammonium chloride solution (90 mL) and ammonium hydroxide (10 mL), and the organic compound was extracted into diethyl ether (3×50 mL). The combined organic extracts were successively washed with a saturated aqueous sodium thiosulfate solution (1×100 mL) and a saturated aqueous sodium chloride solution (1×100 mL). The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 19/1 hexanes/diethyl ether) afforded (E)-2-iodo-pentenoic acid methyl ester (2.9 g, 67%) as a colorless oil: EI-HRMS m/e calcd for C6H9IO2 (M+) 239.9647, found 239.9646.

1. customto obtain a clear solution
2. temperatureThe reaction mixture was cooled to −70° C.
3. additionAfter addition
4. temperatureto warm to −30° C. where it
5. stirringwas stirred for 5 min
6. customThe resulting reaction mixture
7. temperaturewas again cooled back to −70° C.
8. stirringThe reaction mixture was stirred for 4 h at −40° C. to −30° C.
9. temperaturecooled to −70° C. to −60° C., at which time
10. customthe cooling bath was removed
11. temperatureto warm to 25° C. where it
12. stirringwas stirred for 1 h
13. additionThe reaction mixture was then poured into a solution
14. extractionthe organic compound was extracted into diethyl ether (3×50 mL)
15. washThe combined organic extracts were successively washed with a saturated aqueous sodium thiosulfate solution (1×100 mL)
16. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
17. filtrationfiltered
18. concentrationconcentrated in vacuo

ORD record

ord-51001ce600c14b28a9f9fa52483438c4

Source dataset

uspto-grants-2002_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06353111B1