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

Temperatur

-78 °C

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)+.

1. temperatureThe resulting solution was warmed slowly to rt where it
2. stirringstirred for 3 days
3. additionAt the conclusion of this period, the solution was treated with ice-cold saturated aqueous ammonium chloride
4. extractionextracted three times with ethyl acetate
5. dry with materialThe combined organic phases were dried over sodium sulfate
6. concentrationconcentrated under vacuum
7. customto provide an oil
8. customThe oil was purified by column chromatography (silica gel, 20-30% ethyl acetate-hexane)
9. concentrationthe effluent was concentrated
10. customto yield a residue
11. customThe residue was recrystallized from hexane

ORD-Eintrag

ord-afe18c07ef3f4bc58c031913e04f6f32

Quelldatensatz

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08759390B2