Methyl 4-formyl-2-hydroxybenzoate → 2-Hydroxy-4-(1-hydroxy-butyl)-benzoic acid methyl ester

Temperatur

-78 °C

4-Formyl-2-hydroxy-benzoic acid methyl ester (360 mg, 2 mmol) is dissolved in THF (anhydrous, 10 mL). The solution is cooled to −78° C. and stirred under nitrogen. To this solution is added n-propyl-magnesium chloride (2M in THF, 2 mL, 2 mmol) dropwise via syringe. The reaction mixture is stirred at −78° C. for 1 hour, then gradually warmed to room temperature over 1 hour after which point, the reaction is quenched by adding saturated aqueous ammonium chloride. The resulting mixture is extracted with EtOAc (3×15 mL). The combined organic phase is washed with saturated aqueous NaCl and dried over Na2SO4. After concentration, the crude product is purified with silica gel flash column chromatography (10-20% ethyl acetate in hexanes gradient) to afford 2-hydroxy-4-(1-hydroxy-butyl)-benzoic acid methyl ester as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 10.74 (s, 1H), 7.79 (d, 1H, J=8.4 Hz), 6.95 (d, 1H, J=1.2 Hz), 6.86 (dd, 1H, J=1.6, 8 Hz), 4.67 (t, 1H, J=6.8 Hz), 3.94 (s, 3H), 1.82 (br, 1H), 1.80-1.62 (m, 1H), 1.46-1.28 (m, 2H), 0.93 (t, 3H, J=7.2 Hz).

1. stirringThe reaction mixture is stirred at −78° C. for 1 hour
2. temperaturegradually warmed to room temperature over 1 hour after which point
3. customthe reaction is quenched
4. additionby adding saturated aqueous ammonium chloride
5. extractionThe resulting mixture is extracted with EtOAc (3×15 mL)
6. washThe combined organic phase is washed with saturated aqueous NaCl
7. dry with materialdried over Na2SO4
8. concentrationAfter concentration
9. customthe crude product is purified with silica gel flash column chromatography (10-20% ethyl acetate in hexanes gradient)

ORD-Eintrag

ord-6c81a784307c4c34a39befb592a06bd8

Quelldatensatz

uspto-grants-2010_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07816542B2