反应详情

Sodium hydride (60% in oil, 2.1 g, 52 mmol) and methyl 3-oxo-3-o-tolylpropanoate (10 g, 52 mmol) were suspended in tetrahydrofuran and 4-bromo-2-(bromomethyl)-1-fluoro-benzene (15.3 g, 57 mmol) was added. After complete conversion, the mixture was quenched with ice and a saturated solution of ammonium chloride and extracted with n-heptane. The combined organic layers were washed once with a saturated solution of ammonium chloride, water and brine. The organic layer was dried over magnesium sulfate and evaporated to dryness. The obtained yellow oil was dissolved in 25 ml of acetic acid, 25 ml of concentrated hydrochloric acid and 20 ml of 1,4-dioxane and heated under reflux for 4 h until LC/MS showed consumption of the starting material. 50 ml of water and 100 ml of tert-butyl methyl ether were added and the product was extracted. The combined organic layers were washed once with saturated solution of ammonium chloride, water and brine. The organic layer was dried over magnesium sulfate and evaporated to dryness. The residue was purified by column chromatography (silica gel, heptane/ethyl acetate gradient) to give 11.2 g of 3-(5-bromo-2-fluoro-phenyl)-1-o-tolyl-propan-1-one as a colorless oil.

1. customAfter complete conversion, the mixture was quenched with ice
2. extractiona saturated solution of ammonium chloride and extracted with n-heptane
3. washThe combined organic layers were washed once with a saturated solution of ammonium chloride, water and brine
4. dry with materialThe organic layer was dried over magnesium sulfate
5. customevaporated to dryness
6. dissolutionThe obtained yellow oil was dissolved in 25 ml of acetic acid
7. temperature25 ml of concentrated hydrochloric acid and 20 ml of 1,4-dioxane and heated
8. temperatureunder reflux for 4 h until LC/MS
9. customconsumption of the starting material
10. addition50 ml of water and 100 ml of tert-butyl methyl ether were added
11. extractionthe product was extracted
12. washThe combined organic layers were washed once with saturated solution of ammonium chloride, water and brine
13. dry with materialThe organic layer was dried over magnesium sulfate
14. customevaporated to dryness
15. customThe residue was purified by column chromatography (silica gel, heptane/ethyl acetate gradient)