Reaction #2286285

Reaction equation

(3-chloro-4-hydroxy-5-methyl-phenyl)-acetonitrile

(3-Chloro-4-hydroxy-5-methyl-phenyl)-acetonitrile

ethylene glycol dimethyl ether

potassium hydroxide

→

(3-chloro-4-hydroxy-5-methyl-phenyl)-acetic acid

Yield 98.3%

(3-Chloro-4-hydroxy-5-methyl-phenyl)-acetic acid

Yield 98.3%

Solvents

water

Conditions

Workup

1. 1
   TemperatureThe reaction mixture was heated
2. 2
   Temperatureto reflux for 24 h
3. 3
   ConcentrationAt this time, the reaction mixture was concentrated under vacuum
4. 4
   workup.ADDITIONThe resulting solid was diluted with water (100 mL)
5. 5
   Extractionextracted with ethyl acetate (2×50 mL)
6. 6
   workup.ADDITIONThe water layer was acidified to pH=2 by the addition of a 1N aqueous hydrochloric acid solution
7. 7
   Extractionwas extracted with ethyl acetate (2×50 mL)
8. 8
   Washwashed with a saturated aqueous sodium chloride solution (50 mL)
9. 9
   Dryingdried with magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated under vacuum
12. 12
    OtherThe resulting solid was dried under high vacuum overnight

Procedure

A suspension of (3-chloro-4-hydroxy-5-methyl-phenyl)-acetonitrile (4b) (1.3 g, 0.0071 mol) in water (2.06 mL) was treated with ethylene glycol dimethyl ether (13.93 mL, 0.133 mol) followed by potassium hydroxide (2.8 g, 0.0071 mol). The reaction mixture was heated to reflux for 24 h. At this time, the reaction mixture was concentrated under vacuum. The resulting solid was diluted with water (100 mL) and extracted with ethyl acetate (2×50 mL). The organic layers were discarded. The water layer was acidified to pH=2 by the addition of a 1N aqueous hydrochloric acid solution and was extracted with ethyl acetate (2×50 mL). The organic layers were combined, washed with a saturated aqueous sodium chloride solution (50 mL), dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting solid was dried under high vacuum overnight to afford (3-chloro-4-hydroxy-5-methyl-phenyl)-acetic acid (5b) (1.4 g, 97%) as a white solid; EI(+)-HRMS m/z calcd for C9H9ClO3 (M+) 200.0240, found 200.0247. Molecular Weight=200.6233; Exact Mass=200.0240

Source