Acetone → 4-(6-Chloro-2-methylpyridin-3-yl)-2-methylbut-3-yn-2-ol

Participants

Reaction Conditions

Reaction Steps

6-Chloro-3-ethynyl-2-methylpyridine (Example 432, Step 1) (200 mg, 1.32 mmol) was taken up in 4 ml tert-butyl methyl ether and added to a dry flask under argon. The flask was cooled to −78° C. and allowed to stir for 20 min. Butyllithium (0.99 ml of 1.6 M in hexanes, 1.58 mmol) was added to the reaction mixture dropwise over 30 minutes, and the mixture was allowed to stir as such for 30 min. Acetone (0.13 ml, 1.72 mmol) was taken up in 1 ml tert-butyl methyl ether and added dropwise over 30 min. The reaction mixture was allowed to warm to 0° C. and was stirred as such for 90 minutes. The reaction mixture was then allowed to warm to room temperature and stirred for 1 hour. The reaction mixture was quenched with aqueous sodium bicarbonate and extracted twice with diethyl ether. All organic fractions were combined, dried over anhydrous magnesium sulfate, filtered, and concentrated. The resulting crude product was purified by silica gel chromatography (0-50% ethyl acetate/hexanes) to afford the title compound.

Provenance & Evidence