Sodium hydride → 1-((2-(2,4-Difluorophenyl)-3-methyloxiran-2-yl)methyl)-1H-1,2,4-triazole, (2R-cis)-

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Reaction Steps

First, 0.21 g (5.10 mmol) of sodium hydride (60% content) was suspended in 3 mL of DMF, and the resulting suspension was cooled in ice. A solution of 0.53 g (2.19 mmol) of (2R,3R)-1-chloro-2-(2,4-difluorophenyl)butane-2,3-diol in 5 mL of DMF was added thereto, and stirring was performed for 1 hour. A solution of 0.64 g (2.85 mmol) of 1-(p-toluenesulfonyl)-1,2,4-triazole and 0.06 g (0.88 mmol) of triazole in 3 mL of DMF was added, and the reaction solution was stirred at 60° C. for 3 hours. Then, the resulting solution was cooled to room temperature, and 10 mL of water was added to stop the reaction. The resulting product was extracted with ethyl acetate (20 mL×2), and concentration was performed under reduced pressure. A quantitative analysis was performed by HPLC. Thereby, the title compound was obtained in a yield of 43% (HPLC conditions, column: CAPCELL PAK C18 TYPE MG manufactured by Shiseido Co. Ltd., mobile phase: acetonitrile/20 mM (potassium) phosphate buffer solution (pH=2.5)=2/8, flow rate: 1.0 mL/min, column temperature: 30° C., detector: UV 210 nm, retention time: 37 minutes). 1H-NMR (400 MHz, CDCl3) δ: 1.64 (d, 3H, J=5.6 Hz), 3.19 (q, 1H, J=5.6 Hz), 4.42 (d, 1H, J=14.6 Hz), 4.87 (d, 1H, J=14.6 Hz), 6.69-6.80 (m, 2H), 6.98-7.03 (m, 1H), 7.81 (s, 1H), 7.98 (s, 1H).

Provenance & Evidence