Sodium Hydroxide → 5-Iodo-2-(tetrahydro-pyran-4-yl)-pyridin-4-ylamine

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Reaction Steps

To a stirred solution of 5.80 g (32.5 mmol) 2-(tetrahydro-pyran-4-yl)-pyridin-4-ylamine in 20 ml 65% aqueous sulfuric acid heated to 135° C. was added 7.66 g (35.8 mmol) potassium iodate and stirring continued for 2.5 h at 135° C. The mixture was then cooled in an ice-bath before being made basic by addition of 5 N aqueous sodium hydroxide solution. The mixture was extracted three times with tetrahydrofuran and the combined organic phases were dried over sodium sulfate and concentrated in vacuo. The residue was resuspended in 200 ml tetrahydrofuran and 200 ml ethyl acetate and then concentrated in vacuo to 70 ml. The resulting crystals were collected by filtration to afford 2.68 g (27%) 5-iodo-2-(tetrahydro-pyran-4-yl)-pyridin-4-ylamine as a white crystalline solid. ES-MS m/e (%): 305 (M+H+, 100). The mother liquor was concentrated in vacuo; flash chromatography (methanol/dichloromethane 1/50 to 1/20) afforded a further 0.79 g (8%) 5-iodo-2-(tetrahydro-pyran-4-yl)-pyridin-4-ylamine as a white crystalline solid, as well as 0.98 g (10%) 3-iodo-2-(tetrahydro-pyran-4-yl)-pyridin-4-ylamine as a white crystalline solid. ES-MS m/e (%): 305 (M+H+, 100).

Provenance & Evidence