Sodium Hydroxide → 3-Fluoro-4-sulfamoylphenylhydrazine hydrochloride

Temperature

-20 °C

To a stirred suspension of 4-Amino-2-fluoro-benzenesulfonamide (15.2 g, 80 mmol) in concentrated hydrochloric acid solution (180 ml) was slowly added NaNO2 (5.8 g, 84 mmol) in water (180 ml), while maintaining the internal temperature between −15° C. and −20° C. in a dry ice/acetonitrile bath. After the reaction mixture was stirred at −20° C. for 30 minutes, a solution of tin chloride (SnCl2) hydrate (90.3 g, 400 mmol) in concentrated hydrochloric acid solution (100 ml) was added dropwise, and the reaction mixture temperature was maintained between −5° C. and −10° C. with an ice/methanol bath. The stirring was continued at −10° C. for 1 hour and then at room temperature for 4 hours. The pH of the solution was adjusted to 8 by addition of 5 N NaOH solution at 0° C., and the precipitate was removed by filtration through celite. The aqueous layer was extracted with tetrahydrofuran (3×600 ml), and the combined organic layers were washed with brine, dried over magnesium sulfate (MgSO4), and concentrated in vacuo. The residue was dissolved in 10% methanolic HCl solution, followed by stirring at room temperature for 1 hour. The title compound was collected by filtration (12.5 g, 65%).

1. temperaturewhile maintaining the internal temperature between −15° C. and −20° C. in a dry ice/acetonitrile bath
2. temperaturethe reaction mixture temperature was maintained between −5° C. and −10° C. with an ice/methanol bath
3. waitThe stirring was continued at −10° C. for 1 hour
4. waitat room temperature for 4 hours
5. customthe precipitate was removed by filtration through celite
6. extractionThe aqueous layer was extracted with tetrahydrofuran (3×600 ml)
7. washthe combined organic layers were washed with brine
8. dry with materialdried over magnesium sulfate (MgSO4)
9. concentrationconcentrated in vacuo
10. dissolutionThe residue was dissolved in 10% methanolic HCl solution
11. stirringby stirring at room temperature for 1 hour
12. filtrationThe title compound was collected by filtration (12.5 g, 65%)

ORD record

ord-de33ee7a439b458ba38a2ba89d7d33f2

Source dataset

uspto-grants-2005_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06878726B2