Hydrochloric Acid → 5-Bromo-6-chloropicolinic acid

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Reaction Steps

In a 500 ml two-necked-round-bottom flask, 3-bromo-2-chloro-6-methylpyridine (CAN 185017-72-5) (4.0 g, 19.4 mmol) was suspended in H2O (160 ml) to give a colorless suspension. Under stirring, sodium dodecyl sulfate (64 mg, 222 μmol) and KMnO4 (9.19 g, 58.1 mmol) were added. The reaction mixture was stirred at 100° C. for 18 h. The reaction was then cooled to RT and 100 ml NaHSO3-solution (40%) was added dropwise under ice bath-cooling (decolorization). A white precipitate formed and the mixture was stirred a further 30 min. The reaction mixture was acidified with 120 ml 2N-HCl followed by extraction with ethyl acetate (2×200 ml). The combined organic layer was dried over Na2SO4, filtered off and concentrated in vacuo to give a white solid containing a mixture of starting material and the product. The solid was dissolved in 50 ml TBME/THF 9:1 and under stirring was added 15 ml 2N—NaOH which formed a suspension. The suspension was then extracted with 100 ml water. The water-layer was washed with 50 ml TBME. The water-layer was acidified with 20 ml 2N-HCl which was then extracted with a mixture TBME/THF 9:1 (2×50 ml). The combined organic layers were dried over Na2SO4, filtered off and concentrated in vacuo to dryness to give the title compound (1.8 g, 39%) as a white solid; MS (LC/MS): 235.9[M−H]−.

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