Hydrochloric Acid → ethyl 1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate

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Reaction Conditions

Reaction Steps

To a solution of ethyl 1-(2,3-difluorobenzyl)-4-hydroxy-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (9.0 g, 24.69 mmol) in acetonitrile (120 mL) was added pyridine (2.60 mL, 32.1 mmol) and the mixture was cooled to 0° C., then triflic anhydride (5.42 mL, 32.1 mmol) was added dropwise in ˜15 min. After stirring at ambient temperature for 1.5 h the mixture was charged with sodium iodide (18.50 g, 123 mmol) and hydrochloric acid (10.70 mL, 32.1 mmol) (3M/water) and heated to 70° for 1.5 h. The mixture was allowed to cool to ambient temperature and then 20% Na2S2O3/water (350 mL) was added followed by ice-water and the mixture was stirred for 30 min then filtered. The solid was washed with water and dried in vacuo for 18 h to provide ethyl 1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carboxylate (10 g, 19.73 mmol, 80% yield) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.45 (t, J=7.12 Hz, 3 H), 2.66 (s, 3 H), 4.48 (q, J=7.22 Hz, 2 H), 5.53 (s, 2 H), 6.39 (d, J=3.71 Hz, 1 H), 6.75-6.89 (m, 1 H), 6.97 (m, J=8.02, 8.02, 4.93, 1.66 Hz, 1H), 7.03-7.16 (m, 1 H), 7.22 (d, J=3.71 Hz, 1 H); LCMS (m/z) ES+=457 (M+1).

Provenance & Evidence