Sodium Iodide → 8-(6-Chloro-2-iodopyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane

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Reaction Conditions

Reaction Steps

In a 250 mL round-bottomed flask was placed 8-(2,6-dichloropyrimidin-4-yl)-3-oxa-8-azabicyclo[3.2.1]octane (34, 980 mg, 3.77 mmol) in chloroform (4 ml) to give a very light yellow solution. Sodium iodide (941 mg, 6.28 mmol) was added to give a suspension. The mixture was cooled to 0° C. and an aqueous solution (57% w/w) of hydrogen iodide (4.97 ml, 37.7 mmol) was added, resulting in a yellow precipitate. The mixture was slowly warmed to room temperature and stirred at room temperature for 4 h. The mixture was diluted with water and quenched with NaOH (5M) to pH˜8. Aqueous sodium thiosulfate was added to decolorize. The mixture was extracted with dichloromethane, dried over MgSO4 and concentrated. The crude product was added to a silica gel column and was eluted with ethyl acetate in hexanes (10-40%). Collected fractions were concentrated to give the title compound (516 mg) as a white solid. LCMS analysis revealed that the product contained ˜20% starting material. The mixture was used without further purification in the next step.

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