Methanol → Methyl 4-chloro-5-iodo-2-methylbenzoate
Reaction equation
[Cl:1][C:2]1[C:10]([I:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([CH3:12])[CH:3]=1.S(=O)(=O)(O)O.[CH3:18]O>>[Cl:1][C:2]1[C:10]([I:11])=[CH:9][C:5]([C:6]([O:8][CH3:18])=[O:7])=[C:4]([CH3:12])[CH:3]=1Participants
4
Conditions
- Temperature
- 75 °C
Procedure
To a solution of 4-chloro-5-iodo-2-methylbenzoic acid (compound 177.1, 20.0 g, 67.5 mmol, 1.00 equiv) in methanol (100 mL) was added sulfuric acid (5 mL) dropwise. The resulting mixture was stirred overnight at 75° C. After cooling to ambient temperature, the methanol was removed under reduced pressure. The pH value of the remaining aqueous layer was carefully adjusted to 7 with sodium bicarbonate (aq., 1 M. Note: significant gas evolution). The aqueous phase was extracted with 2×200 mL of ethyl acetate and the combined organic layers were washed with 2×100 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:50) as eluent to furnish 20.0 g (95%) of methyl 4-chloro-5-iodo-2-methylbenzoate as a light yellow liquid.