Iodine → Methyl 4-fluoro-2-iodo-6-methylbenzoate

Participants

Reaction Conditions

Reaction Steps

4-Fluoro-2-methylbenzoic acid (5.0 gr, 32.4 mmol), palladium(II) acetate (0.364 g, 1.62 mmol), iodobenzene diacetate (12.54 g, 38.92 mmol) and elemental iodine (9.88 g, 38.92 mmol) were dissolved in N,N-dimethylformamide (130 mL) and stirred at 100° C. overnight. The reaction mixture was cooled to room temperature, diluted with methyl-tert-butylether and aqueous hydrochloric acid and washed with 10% sodium metabisolfite aqueous solution. Organic phase was treated with 2N aqueous sodium hydroxide. The resulting aqueous phase was treated with aqueous hydrochloric acid up to acidic pH and extracted with methyl-tert-butylether. The organic phase was washed with brine, dried over sodium sulfate and concentrated. So obtained iodinated benzoic acid (6.9 g, 24.6 mmol) was dissolved in N,N-dimethylformamide (50 mL) and methyliodide (3 mL, 49.2 mmol) and potassium carbonate (5 g, 36.9 mmol) were added. The reaction mixture was stirred overnight at room temperature, diluted with methyl-tert-butylether and washed with water, 1M sodium hydroxide, water and brine. Solvent was removed under reduced pressure and the crude was purified by flash chromatography (n-hexane/diethyl ether 100:2) to give title compound (5.9 g, 63% yield).

Provenance & Evidence