Ethanol → 2-[4-(3,4-dihydro-2H-1-benzopyran-6-yl)-2,5-dimethyl thiophen-3-yl]-2-oxoacetic acid

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Reaction Conditions

Reaction Steps

A solution of ethyl 2-(4-bromo-2,5-dimethylthiophen-3-yl)-2-oxoacetate (17c) (1.0 g, 3.43 mmol), sodium carbonate (1.46 g, 13.7 mmol), and 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman (1.16 g, 4.46 mmol) in a mixture of toluene (9 mL), ethanol (3 mL) and water (3.5 mL) was bubbled with nitrogen for 5 minutes. Palladium tetrakis(triphenylphosphine) (0.2 g, 0.17 mmol) was added and the reaction mixture was heated at 95° C. overnight. Water (5 mL) was added and the organic layer was extracted with 1N sodium hydroxide (5 mL). The combined aqueous layers were washed with ethyl acetate (10 mL), acidified with 1M hydrochloric acid until pH 2 and extracted with dichloromethane (2×10 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo to provide the desired product (42a) (1.09 g, 3.43 mmol, 100%) which was used without further purification.

Provenance & Evidence