Reaktion #363371

Reaktionsgleichung

(E)-3-cyclooctyl-2-iodo-acrylic acid methyl ester

trimethylsilyl chloride

4-bromophenyl methyl sulfone

ammonium chloride

triphenylphosphine

1,2-dibromoethane

→

(E)-3-cyclooctyl-2-(4-(methanesulfonyl)-phenyl)-acrylic acid methyl ester

Ausbeute 90.4%

Lösungsmittel

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturto cool
2. 2
   Temperaturheated again
3. 3
   workup.STIRRINGThe reaction mixture was then stirred at 40-45° C. for 1 h
4. 4
   workup.STIRRINGstirred overnight at 25° C
5. 5
   Sonstige(˜2 h)
6. 6
   workup.STIRRINGwas stirred at 25° C. under argon for 10 min
7. 7
   TemperaturThe resulting brick red solution was heated at 50° C. for 24 h The reaction mixture
8. 8
   Temperaturwas cooled to 25° C.
9. 9
   Extraktionthe organic compound was extracted into ethyl acetate (3×75 mL)
10. 10
    WaschenThe combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×200 mL)
11. 11
    Trocknendried over anhydrous magnesium sulfate
12. 12
    Filtrationfiltered
13. 13
    Einengenconcentrated in vacuo

Vorschrift

A mixture of zinc dust (1.3 g, 20 mmol, Aldrich, −325 mesh) and dry tetrahydrofuran (3 mL) under argon was treated with 1,2-dibromoethane (0.38 g, 2 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 (220 mg, 2 mmol), and the suspension was stirred for 15 min at 25° C. The reaction mixture was then treated dropwise with a solution of (E)-3-cyclooctyl-2-iodo-acrylic acid methyl ester (3.22 g, 10 mmol) in dry tetrahydrofuran (4 mL) over 10 min. The reaction mixture was then stirred at 40-45° C. for 1 h and then stirred overnight at 25° C. The reaction mixture was then diluted with dry tetrahydrofuran (8 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) (135 mg, 0.25 mmol) and triphenylphosphine (260 mg, 1 mmol) in dry tetrahydrofuran (10 mL) was stirred at 25° C. under argon for 10 min and then treated with 4-bromophenyl methyl sulfone (2.12 g, 9 mmol) and the freshly prepared zinc compound in tetrahydrofuran. The resulting brick red solution was heated at 50° C. for 24 h The reaction mixture was cooled to 25° C. and then poured into a saturated aqueous ammonium chloride solution (100 mL), and the organic compound was extracted into ethyl acetate (3×75 mL). The combined organic extracts were washed with a saturated aqueous sodium chloride solution (1×200 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 4/1 to 1/1 hexanes/ethyl acetate) afforded (E)-3-cyclooctyl-2-(4-(methanesulfonyl)-phenyl)-acrylic acid methyl ester (2.85 g, 90%) as a light yellow semi-solid: EI-HRMS m/e calcd for C19H26O4S (M+) 350.1552, found 350.1554.

Quelle