Hydrochloric Acid → 2-(4-Octyloxyphenyl)-5-hydroxy-6-fluoropyridine

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Reaction Steps

4.3 ml (8.6 mmol) of a 2-molar lithium diisopropylamide solution in tetrahydrofuran/hexane/ethylbenzene are added dropwise at -78° C. to 2.36 g (7.8 mmol) of 2-fluoro-6-(4-octyloxyphenyl)pyridine (prepared as described in Example 2) in 180 ml of tetrahydrofuran, and the mixture is stirred for 4 hours. 2.95 g (17.2 mmol) of triisopropyl borate in 10 ml of tetrahydrofuran are then added dropwise at -78° C., and the reaction mixture is stirred overnight, during which it warms to room temperature. After addition of 12.0 ml of 10% hydrochloric acid and stirring at room temperature for i hour, sodium chloride solution is added, the mixture is extracted with ether, the ether phase is washed with sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue is taken up in 40 ml of ether, and the resulting mixture is heated to boiling. 8.03 g (23.5 mmol) of a 10% hydrogen peroxide solution are added dropwise, and the reaction mixture is refluxed for 4 hours. After separating off the ether phase, the aqueous phase is extracted with ether. The combined ether phases are washed with sodium sulfite solution and then with sodium chloride solution, dried over sodium sulfate, filtered and evaporated to dryness. Purification of the residue by chromatography (silica gel, 7:3 hexane/ethyl acetate) gives 1.13 g of 2-fluoro-3-hydroxy-6-(4-octyloxyphenyl)pyridine. ##STR18##

Provenance & Evidence