tert-Butyl acetate → Tert-butyl 3-(2-hydroxy-5-methoxyphenyl)-3-oxopropanoate

Participants

Reaction Conditions

Reaction Steps

A solution of lithium bis(trimethylsilyl)amide (1.0 M in tetrahydrofuran, 61.5 mL, 61.5 mmol) was stirred at −78° C. and treated over a 5 min period with a solution of tert-butyl acetate (5.2 mL, 38.4 mmol) in tetrahydrofuran (13 mL). The resulting mixture was stirred at −78° C. for 55 min, and then treated dropwise with a solution of methyl 2-hydroxy-5-methoxybenzoate (1.63 mL, 10.98 mmol) in tetrahydrofuran (13 mL) over a 5 min period. The resulting solution was warmed slowly to rt where it stirred for 3 days. At the conclusion of this period, the solution was treated with ice-cold saturated aqueous ammonium chloride, and then extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated under vacuum to provide an oil. The oil was purified by column chromatography (silica gel, 20-30% ethyl acetate-hexane), and the effluent was concentrated to yield a residue. The residue was recrystallized from hexane to provide tert-butyl 3-(2-hydroxy-5-methoxyphenyl)-3-oxopropanoate as yellow crystals (2.40 g, 82%). 1H NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 9 H) 3.79 (s, 3 H) 3.89 (s, 2 H) 6.95 (d, J=9.2 Hz, 1 H) 7.11 (d, J=3.1 Hz, 1 H) 7.14 (dd, J=8.6, 2.5 Hz, 1 H) 11.54 (s, 1 H). Mass spectrum m/z 289.19 (M+Na)+.

Provenance & Evidence