Reaction #2286286

Reaction equation

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

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

sulfuric acid

methanol

→

acetic acid methyl ester

Yield 91.0%

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

Yield 91.0%

Conditions

Workup

1. 1
   ConcentrationAt this time, the reaction mixture was concentrated under vacuum
2. 2
   workup.ADDITIONThe resulting oil was diluted with ethyl acetate (100 mL)
3. 3
   WashThe organics were washed with water (2×50 mL)
4. 4
   Dryingdried with magnesium sulfate
5. 5
   Filtrationfiltered
6. 6
   Concentrationconcentrated
7. 7
   OtherThe resulting residue was purified by column chromatography
8. 8
   Washeluted with 10% ethyl acetate in petroleum ether

Procedure

A solution of (3-chloro-4-hydroxy-5-methyl-phenyl)-acetic acid (5b) (1.4 g, 6.98 mmol) in methanol (60 mL) was treated with concentrated sulfuric acid (0.5 mL) at room temperature under argon. The reaction mixture was heated to 70° C. for 24 h. At this time, the reaction mixture was concentrated under vacuum. The resulting oil was diluted with ethyl acetate (100 mL). The organics were washed with water (2×50 mL), dried with magnesium sulfate, filtered and concentrated. The resulting residue was purified by column chromatography using silica gel eluted with 10% ethyl acetate in petroleum ether to afford 3-chloro-4-hydroxy-5-methyl-phenyl)-acetic acid methyl ester (6b) (1.36 g, 91%) as a white solid; EI(+)-HRMS m/z calcd for C10H11ClO3 (M+) 214.0397, found 214.0400. Molecular Weight=214.6504; Exact Mass=214.0397

Source