5-Amino-2-fluoropyridine → (2S,4S)-Benzyl 2-(6-fluoropyridin-3-ylcarbamoyl)-4-methoxypyrrolidine-1-carboxylate

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Reaction Steps

To a solution of 6-fluoropyridin-3-amine (500 mg, 4.46 mmol) in THF (15 mL) was added isopropylmagnesium chloride (2.0 M THF solution, 2.12 mL, 4.24 mmol) dropwise at 0° C. The resulting reaction mixture was stirred at room temperature for 30 min. A solution of (2S,4S)-1-benzyl 2-methyl 4-methoxypyrrolidine-1,2-dicarboxylate 18B (435 mg, 1.49 mmol) in THF (2 mL) was added to the reaction mixture. The reaction mixture was stirred at room temperature for 4 h and quenched with methanol (3 mL). The crude product was purified by prep. HPLC to give (2S,4S)-benzyl 4-methoxy-2-(pyrazin-2-ylcarbamoyl)pyrrolidine-1-carboxylate 62A (424 mg, 80%) as an oil. LC/MS [M+H-Boc]+: 240; Ret time (Method F): 2.43 min.

Provenance & Evidence