Hydrochloric Acid → 2,2-Dimethyl-3-phenylpropanoic acid

Participants

Reaction Conditions

Reaction Steps

Hexamethyldisilazane (34 g, 0.21 mol) was dissolved in tetrahydrofuran (280 mL), and 1.67M n-butyllithium in hexane (127 mL, 0.21 mol) was added dropwise at −78° C. The reaction solution was warmed to 0° C. over 1 hour and then cooled to −78° C. again. Benzyl isobutyrate (25 g, 0.14 mol) in tetrahydrofuran (70 mL) was added dropwise, and the reaction solution was stirred at −78° C. for 1 hour. Chlorotrimethylsilane (36 mL, 0.12 mol) was further added dropwise at the same temperature, and the reaction solution was stirred for 1 hour, then warmed to room temperature and stirred for 19 hours. After completion of the reaction, the solvent was partially removed from the reaction solution under reduced pressure, and the resulting white suspension was diluted with hexane (200 mL) and filtered through Celite under a nitrogen atmosphere to remove the white solid from the reaction solution. The filtrate was distiled under reduced pressure, and the resulting pale yellow oil was heated at 100° C. for 2 hours to give a brown oil. The brown oil was mixed with 10 mL of 1 M hydrochloric acid and stirred at 60° C. for 4 hours, neutralized with saturated aqueous sodium hydrogen carbonate and extracted with ethyl acetate (100 mL×2) and chloroform (100 mL×2). The resulting organic layer was concentrated, and the resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel 80 g, ethyl acetate 100%) to give 8.41 g of the desired product as white crystals.

Provenance & Evidence