Lithium Hexamethyldisilazide → 3-cyano-N-(2,4-dimethoxybenzyl)-4-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide

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Reaction Conditions

Reaction Steps

N-(2,4-Dimethoxybenzyl)-1,3,4-thiadiazol-2-amine (Preparation 14, 5.72 g, 22.8 mmol) was dissolved in 2-methyltetrahydrofuran (100 mL) and the suspension cooled to −50° C. A 1M solution of lithium bis(trimethylsilyl)amide in tetrahydrofuran (34.1 mL, 34.1 mmol) was added slowly over 15 minutes. This suspension was stirred at −50° C. for 5 minutes, warmed to 10° C. then cooled again to −78° C. A solution of 3-cyano-4-fluorobenzene-1-sulfonyl chloride (10 g, 45.5 mmol) in tetrahydrofuran (20 mL) was then added drop wise. The pale orange solution was allowed to warmed to 20° C. for 18 hours. The reaction was quenched with an aqueous solution of saturated ammonium chloride (50 mL) and stirred vigorously for 5 minutes. Ethyl acetate (100 mL) was added and the layers separated. The organic layer was washed with water (100 mL) and concentrated in vacuo to give an orange gum. The gum was dissolved in ethyl acetate and eluted through a silica plug before being purified by silica gel column chromatography (ISCO™, 50% ethyl acetate in heptane) to afford the title compound as a pale yellow oil (2.96 g).

Provenance & Evidence