Lithium bis(trimethylsilyl)amide → HCID 66652613, compound

Participants

Reaction Steps

To a nitrogen purged solution of N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine (Preparation 18, 448 mg, 1.78 mmol) in tetrahydrofuran (7.5 mL) at −78° C. was added lithium hexamethyl disilazane (1.0 M in tetrahydrofuran, 1.96 mL). The reaction was stirred for 15 minutes before a solution of 4-bromo-3-cyanobenzenesulfonyl chloride (Preparation 27, 500 mg, 1.78 mmol) in tetrahydrofuran (7.5 mL) was added dropwise. The reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was partitioned between water (10 mL) and ethyl acetate (3×10 mL). The combined organic extracts were washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a yellow solid. The material was purified by silica gel column chromatography (ISCO™ companion, 40 g column, 0-30% ethyl acetate in heptane gradient elution). Fractions containing product were combined and concentrated in vacuo to obtain the title compound as a colourless solid (883 mg, 73%)

Provenance & Evidence