反应详情

温度

-10 °C

The crude 2-(4-tert-butyl-benzenesulfonylamino)-5-chloro-4-fluoro-benzoyl chloride (57.0 mmol) was dissolved in dichloromethane (100 mL) and transferred to an addition funnel. Anhydrous hydrazine (44 mL, 1.38 mol), dissolved in 300 mL dichloromethane in a one liter Erlenmeyer flask, was cooled to −10° C. in a dry ice-acetone bath and the acyl chloride solution was added in a slow stream to the stirring hydrazine solution over a 15 minute period. The cold bath was subsequently removed following the addition and LCMS analysis at 15 minutes indicated the reaction was complete. The resultant reaction mixture was quenched with water (200 mL), resulting in a voluminous white precipitate that was collected by vacuum filtration. The precipitate was slurried in 500 mL ethyl acetate and acetic acid was added while stirring until a homogeneous solution was formed. The solution was transferred to a separatory funnel and extracted with 2×50 mL of water. The aqueous phases were discarded and the organic phase was dried over sodium sulfate, filtered, and concentrated in vacuo to produce 4-tert-butyl-N-(4-chloro-5-fluoro-2-hydrazinocarbonyl-phenyl)-benzenesulfonamide (16 g) in a 71% yield: HPLC retention time=2.63 minutes; MS (ES) M+H expected 400.0, found 400.0.

1. customtransferred to an addition funnel
2. customThe cold bath was subsequently removed
3. additionthe addition and LCMS analysis at 15 minutes
4. customThe resultant reaction mixture
5. customwas quenched with water (200 mL)
6. customresulting in a voluminous white precipitate that
7. filtrationwas collected by vacuum filtration
8. additionacetic acid was added
9. customwas formed
10. customThe solution was transferred to a separatory funnel
11. extractionextracted with 2×50 mL of water
12. dry with materialthe organic phase was dried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated in vacuo