Diisopropylamine → (2,3,4-Trimethoxy-6-methylphenyl)(2-fluoro-4-iodo-5-methyl-3-pyridyl)methanol

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Reaction Steps

8.90 ml (1.57 mol/l hexane solution) was dropwise added at −78° C. to a solution having 1.34 g (13.3 mmol) of diisopropylamine dissolved in 27 ml of tetrahydrofuran, followed by stirring for 30 minutes. To this solution, a solution having 3.15 g (13.3 mmol) of 2-fluoro-3-iodo-5-methylpyridine obtained in Step (a) dissolved in 5 ml of tetrahydrofuran was added, followed by stirring for 1 hour, so that 2-fluoro-3-iodo-5-methyl-4-pyridyllithium formed at the initial stage was isomerized to 2-fluoro-4-iodo-5-methyl-3-pyridyllithium. To the reaction mixture, a solution having 2.79 g (13.3 mmol) of 2,3,4-trimethoxy-6-methylbenzaldehyde dissolved in 5 ml of tetrahydrofuran was added, followed by stirring for 2 hours. After the temperature was increased to room temperature, 50 ml of water was added, followed by extraction with ethyl ether. The organic layer was dried over magnesium sulfate and subjected to filtration, the solvent was distilled off under reduced pressure, and the obtained crude product was purified by silica gel chromatography to obtain 4.45 g (yield: 75%) of (2,3,4-trimethoxy-6-methylphenyl)(2-fluoro-4-iodo-5-methyl-3-pyridyl)methanol.

Provenance & Evidence