Sodium Carbonate → 5-Methoxy-[2-(4-fluorophenyl)] benzoic acid methyl ester

참여 물질

반응 단계

Methyl-2-bromo-5-methoxybenzoate (15.1 g; 0.062 mol), 4-fluorobenzene boronic acid (9.98 g; 0.0713 mol), and tris (dibenzylideneacetone)dipalladium (0) (1.0 g) were dissolved in 100 mL dimethoxyethane (DME) and 100 mL 2N sodium carbonate and stirred at reflux overnight. The reaction mixture was cooled, the DME removed in vacuo, and the resulting oil partitioned between methylene chloride and water. The aqueous layer was extracted further with methylene chloride and the combined organic extracts dried over magnesium sulfate and concentrated in vacuo. Purification of the crude material by silica gel column chromatography (gradient elution with ethyl acetate/hexane) provided 5-methoxy-[2-(4-fluorophenyl)] benzoic acid methyl ester as a colorless oil (63%). The ester (8.6 g) was hydrolyzed in refluxing 1N sodium hydroxide (72 mL) and ethanol (250 mL). The reaction mixture was cooled and extracted with ethyl acetate. The aqueous layer was then acidified, extracted with EtOAc and the extracts concentrated to afford pure 5-methoxy-[2-(4-fluorophenyl)] benzoic acid in 86% yield. The acid (6.9 g; 0.03 mol) was dissolved in 50 mL thionyl chloride and refluxed overnight. The thionyl chloride was removed in vacuo to afford 2-fluoro-7-methoxy fluorenone quantitatively as an orange solid.

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