Reacción #358330

Ecuación de reacción

(3,5-dimethyl-4-hydroxy-phenyl)-acetonitrile

ethylene glycol dimethyl ether

potassium hydroxide

→

(3,5-dimethyl-4-hydroxy-phenyl)-acetic acid

Rendimiento 5.5%

Disolventes

water

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture was heated
2. 2
   Temperaturato reflux for 2 d
3. 3
   ConcentraciónThe reaction mixture was concentrated under vacuum
4. 4
   workup.ADDITIONThe resulting solid was diluted with water (100 mL)
5. 5
   Extracciónextracted with ethyl acetate (2×75 mL)
6. 6
   workup.ADDITIONThe aqueous layer was acidified to pH=2 by the addition of a 1N aqueous hydrochloric acid solution
7. 7
   Extracciónwas extracted with ethyl acetate (2×100 mL)
8. 8
   Lavadowashed with a saturated aqueous sodium chloride solution (2×50 mL)
9. 9
   Secadodried with magnesium sulfate
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated under vacuum
12. 12
    OtroThe solid was purified by column chromatography
13. 13
    Lavadoeluted with 15-25% ethyl acetate in petroleum ether

Procedimiento

A suspension of (3,5-dimethyl-4-hydroxy-phenyl)-acetonitrile (4a) (550 mg, 0.003 mol) in water (0.98 mL) was treated with ethylene glycol dimethyl ether (6.6 mL, 0.063 mol) followed by potassium hydroxide (1.34 g, 0.024 mol). The reaction mixture was heated to reflux for 2 d. The reaction mixture was concentrated under vacuum. The resulting solid was diluted with water (100 mL) and extracted with ethyl acetate (2×75 mL). The organic layers were discarded. The aqueous layer was acidified to pH=2 by the addition of a 1N aqueous hydrochloric acid solution and was extracted with ethyl acetate (2×100 mL). The organic layers were combined, washed with a saturated aqueous sodium chloride solution (2×50 mL), dried with magnesium sulfate, filtered and concentrated under vacuum. The solid was purified by column chromatography using silica gel eluted with 15-25% ethyl acetate in petroleum ether to afford (3,5-dimethyl-4-hydroxy-phenyl)-acetic acid (5a) (30 mg, 5%) as a yellow solid; EI(+)-HRMS m/z calcd for C10H12O3 (M+) 180.0786, found 180.0782. Molecular Weight=180.2053; Exact Mass=180.0786

Fuente