Acetic Acid → HCID 22241510, compound

Participants

Reaction Conditions

Reaction Steps

[3-(2-Methoxy-ethoxymethoxy)-phenylethynyl]-trimethyl silane (0.57 g, 2 mmol, example 97) and 1.0 M tetrabutylammonium fluoride (2.1 mL, 2 mmol) are added to THF (10 mL) and acetic acid (0.13 g, 2 mmol) is added and this mixture is stirred at 20° C., under nitrogen. After 15 minutes, the solvent is removed in vacuo and the residue is azeotroped with benzene and purified by flash chromatography (silica, 20% ethyl acetate, 30% dichloromethane in hexanes) to give 1-ethynyl-3-(2-methoxy-ethoxymethoxy)-benzene (0.28 g, 1.4 mmol) which is dissolved in THF (8 mL), cooled to −78° C., under nitrogen and to this solution is added 2.5M n-butyl lithium (0.56 mL, 1.4 mmol) dropwise over 30 seconds. After stirring for 15 minutes, 1.0M zinc chloride in ether (1.4 mL, 1.4 mmol) is added dropwise over 30 seconds and this mixture is stirred for 30 minutes. Bis-(dibenzylideneacetone) palladium (0.04 g, 0.07 mmol) and bis (diphenyl phosphino) ferrocene (0.04 g, 0.07 mmol) is added and to this mixture is added ethyl-2-methyl-6-trifluoromethanesulfonyloxy benzoate (0.44 g, 1.4 mmol, 95) in THF (2 mL). The cooling bath is removed and the reaction allowed to warm to room temperature. Then the reaction mixture is heated in an oil bath at 65° C. overnight. The reaction is then diluted with ethyl acetate (50 mL), washed with saturated ammonium chloride and brine and then dried over magnesium sulfate. The solvent is removed in vacuo and the residue purified by flash chromatography (silica, 10% ethyl acetate, 25% dichloromethane in hexanes) to give the title compound. MS (ESI) 369 (M+H)+.

Provenance & Evidence