Sodium Iodide → 3-(6-Chloro-2-iodo-pyrimidin-4-yl)-8-oxa-3-aza-bicyclo[3.2.1]octane

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In a 20 mL scintillation vial was placed 3-(2,6-dichloropyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (9, 780 mg, 3 mmol) in chloroform (2 ml) to give a very light yellow solution. Sodium iodide (749 mg, 5 mmol) was added to give a suspension. The mixture was cooled to 0° C. and an aqueous solution (57% w/w) of hydrogen iodide (0.356 ml, 2.70 mmol) was added, resulting in a thick yellow precipitate. The mixture was stirred at room temperature for 16 hours. LCMS indicated only a trace of product being formed. Additional aqueous. HI (356 μL) was added and the mixture was stirred at room temperature for 64 hours. Additional aqueous HI was added (712 μL) and the suspension was stirred for an additional 7 hours. LCMS showed the presence of the desired product as the main peak along with a dehalogenated impurity and starting material. The mixture was diluted with water and solid K2CO3 was added to pH˜8. The aqueous phase was extracted with dichloromethane. The organic phase was washed with aqueous sodium thiosulfate to decolorize, dried over MgSO4, filtered and concentrated. The crude product was added to a silica gel column and was eluted with ethyl acetate in hexanes (15-40%). Collected fractions were concentrated to give 588 mg (1.7 mmol, 56%) of a white solid, which was a mixture of the desired product containing approximately 20% starting material. The mixture was carried on to the next step.

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