반응 #363405

반응 방정식

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

trimethylsilyl chloride

4-bromophenyl methyl sulfone

ammonium chloride

triphenylphosphine

1,2-dibromoethane

→

(E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid methyl ester

수율 86.0%

용매

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

반응 조건

후처리

1. 1
   온도to cool
2. 2
   온도heated again
3. 3
   workup.ADDITIONAfter the addition
4. 4
   workup.STIRRINGthe reaction mixture was stirred for 1 h at 40-45° C.
5. 5
   workup.STIRRINGstirred overnight at 25° C
6. 6
   기타(˜2 h)
7. 7
   workup.STIRRINGwas stirred at 25° C. under argon for 10 min
8. 8
   온도The resulting brick red solution was heated at 50° C. for 24 h, at which time, thin layer chromatography analysis of the reaction mixture
9. 9
   온도The reaction mixture was cooled to 25° C.
10. 10
    추출the organic compound was extracted into diethyl ether (3×50 mL)
11. 11
    세척The combined ether extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL)
12. 12
    건조dried over anhydrous magnesium sulfate
13. 13
    여과filtered
14. 14
    농축concentrated in vacuo

실험 절차

A mixture of zinc dust (0.98 g, 15 mmol, Aldrich, −325 mesh) and dry tetrahydrofuran (3 mL) under argon was treated with 1,2-dibromoethane (0.14 g, 0.75 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 (82 mg, 0.75 mmol), and the suspension was stirred for 15 min at 25° C. The reaction mixture was then treated dropwise with a solution of (E)-4-cyclopentyl-2-iodo-but-2-enoic acid methyl ester (1.47 g, 5 mmol) in dry tetrahydrofuran (1.5 mL) over 3 min. After the addition, the reaction mixture was stirred for 1 h at 40-45° C. and then stirred overnight at 25° C. The reaction mixture was then diluted with dry tetrahydrofuran (5 mL), and the stirring was stopped to allow the excess zinc dust to settle down (˜2 h). In a separate reaction flask, bis(dibenzylideneacetone)palladium(0) (54 mg, 0.1 mmol) and triphenylphosphine (104 mg, 0.4 mmol) in dry tetrahydrofuran (10 mL) was stirred at 25° C. under argon for 10 min and then treated with 4-bromophenyl methyl sulfone (0.94 g, 4 mmol) and the freshly prepared zinc compound in tetrahydrofuran. The resulting brick red solution was heated at 50° C. for 24 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was cooled to 25° C. and then poured into a saturated aqueous ammonium chloride solution (75 mL), and the organic compound was extracted into diethyl ether (3×50 mL). The combined ether extracts were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 3/7 hexanes/diethyl ether) afforded (E)-4-cyclopentyl-2-(4-methanesulfonyl-phenyl)-but-2-enoic acid methyl ester (1.10 g, 86%) as a colorless oil: EI-HRMS m/e calcd for C17H22O4S (M+) 322.1235, found 322.1239.

출처