Reaction #2286278

Reaction equation

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

ethylene glycol dimethyl ether

potassium hydroxide

→

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

Yield 5.5%

Solvents

water

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was heated
2. 2
   Temperatureto reflux for 2 d
3. 3
   ConcentrationThe reaction mixture was concentrated under vacuum
4. 4
   workup.ADDITIONThe resulting solid was diluted with water (100 mL)
5. 5
   Extractionextracted 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
   Extractionwas extracted with ethyl acetate (2×100 mL)
8. 8
   Washwashed with a saturated aqueous sodium chloride solution (2×50 mL)
9. 9
   Dryingdried with magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated under vacuum
12. 12
    OtherThe solid was purified by column chromatography
13. 13
    Washeluted with 15-25% ethyl acetate in petroleum ether

Procedure

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

Source