HCID 11427516, compound → HCID 19081600, compound

Participants

Reaction Steps

A solution of 1.17 g of 2-(3-bromo-4,5-dimethoxy-phenyl)-5,5-dimethyl-1,3-dioxan (Example 6a)) in 10 ml of tetrahydrofuran is treated dropwise at -100° over 20 minutes with 2.2 ml of a 1.6M n-butyllithium solution in n-hexane. The solution is stirred for a further hour at -100° and then treated dropwise at this temperature with 7 ml of a 0.5M zinc chloride solution in tetrahydrofuran within 20 minutes. The reaction mixture is warmed slowly to 0° and stirred at this temperature for a further 1hr. The solution is then slowly added dropwise through a Teflon tube to a boiling mixture of 1 g of ethyl 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[[(trifluoromethyl)sulphonyl]oxy]quinoline-3-carboxylate (J. Heterocyclic Chem., 28, 1581 (1991)) and 20 mg of tetrakis-triphenylphosphine-palladium in 10 ml of tetrahydrofuran. The mixture is stirred at reflux temperature for a further 2 hrs. it is cooled to room temperature, diluted with 50 ml of ethyl acetate and washed with 50 ml of a saturated aqueous ammonium chloride solution, 50 ml of water and 50 ml of a saturated aqueous sodium chloride solution. The organic phase is dried over magnesium sulphate and concentrated. The residue is chromatographed on silica gel with ethyl acetate. 850 mg (68%) of ethyl 1-cyclopropyl-7-[5-(5,5-dimethyl-1,3-dioxan-2-yl)-2,3-dimethoxy-phenyl]-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylate are isolated as a colourless solid. M.p. 178°-180° after recrystallization from ethyl acetate/n-hexane.

Provenance & Evidence