Carbon tetrabromide → Methyl 1-({5-[5-(3-fluoro-4-isobutylphenyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl}methyl)azetidine-3-carboxylate

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Reaction Steps

{5-[5-(3-Fluoro-4-isobutylphenyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl}methanol (0.16 g, 0.47 mmol) that was obtained in Example 23 (23H), carbon tetrabromide (0.23 g, 0.71 mmol), and triphenylphosphine (0.19 g, 0.71 mmol) were dissolved in dichloromethane (6 ml) at 0° C. and stirred at the same temperature for 10 minutes. After stirring, the reaction mixture was evaporated in vacuo, and the residue obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:6) to afford the reaction intermediate. Subsequently, to a solution of the reaction intermediate obtained in dichloromethane (7 ml) were added successively methyl 3-azetidinecarboxylate hydrochloride (0.11 g, 0.71 mmol) and N,N-diisopropylethylamine (0.25 ml, 1.4 mmol) with stirring, and the resulting mixture was stirred at room temperature for 13 hours. After stirring, a saturated aqueous solution of sodium hydrogencarbonate (2 ml) was added to the reaction mixture to quench the reaction, and the resulting mixture was poured into water (20 ml) and extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After filtration, the filtrate was evaporated in vacuo, and the crude product of the title compound thus obtained was purified by chromatography on a silica gel column using a mixed solvent of ethyl acetate and hexane (1:12) as the eluent to afford the title compound (0.12 g) in a yield of 59% as a white crystalline solid.

Provenance & Evidence