2-Methyltetrahydrofuran → Tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate

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Reaction Steps

Combine tert-butyl 4-[4,5-diiodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate (39 g, 64.97 mmol) and 2-methyltetrahydrofuran (273 mL), then cool to −15° C. Add 2 M isopropylmagnesium chloride in tetrahydrofuran (32.48 mL, 1.0 eq) dropwise over 45 minutes, maintaining the temperature below −10° C. Stir for an additional 30 min. Add acetic acid (7.45 mL) dropwise, then water (120 mL). Wash the aqueous phase with methyl tert-butyl ether (2×50 mL). Wash the organics with aqueous saturated sodium chloride. Dry the organics over anhydrous magnesium sulfate and concentrate in vacuo. Crystallize the resulting oil from hexanes/methyl tert-butyl ether to give tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate as a white solid (29 g, 94%). MS (ES) m/z=475 [M]+.

Provenance & Evidence