Acetone → 4-Hydroxy-4-methyl-pent-2-ynoic acid ethyl ester

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Reaction Steps

To a stirred solution of propynoic acid ethyl ester (20 mL, 197 mmol) in a mixture of 300 mL tetrahydrofuran:ether:pentane (4:1:1 by volume) cooled in a dry ice/isopropanol bath was added n-butyllithium (79 mL, 197 mmol, 2.5 M in hexanes) dropwise. After 15 minutes, anhydrous acetone (13.1 mL, 197 mmol) was slowly added. The reaction was kept below −78° C. for 8 h and quenched with an aqueous ammonium chloride solution, and the resulting mixture was stirred for 5 min. The reaction was warmed up to room temperature and extracted repeatedly with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, and the residue was purified via silica gel column chromatography (0-15% ethyl acetate in heptane) to give the title compound (10.75 g, 68.8 mmol) as a yellow oil.

Provenance & Evidence