N,N-Dimethylsulfamide → 5-chloro-N-(N,N-dimethylsulfamoyl)-2,4-difluorobenzamide

To a mixture of 5-chloro-2,4-difluorobenzoic acid (3.48 g, 18.1 mmol) in anhydrous dichloromethane (100 mL) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (5.20 g, 27.1 mmol), N,N-dimethylpyridin-4-amine (5.04 g, 41.3 mmol), and N,N-dimethylsulfamide (3.37 g, 27.1 mmol) at room temperature. The resulting mixture was stirred at room temperature for 24 h. The mixture was then cooled to 0° C. and quenched with hydrochloride acid (1N, 100 mL) followed by extraction with dichloromethane (2×200 mL). The organic layer was washed with ammonium chloride solution (3×30 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuo and the crude product was crystallized from ethyl acetate and hexanes to afford the title compound as a white solid (1.20 g, 22%): 1H NMR (300 MHz, DMSO-d6) δ 12.05 (s, 1H), 7.98-7.93 (m, 1H), 7.74-7.68 (m, 1H), 2.89 (s, 6H); MS (ES−) m/z 297.1, 299.1 (M−1).

1. temperatureThe mixture was then cooled to 0° C.
2. customquenched with hydrochloride acid (1N, 100 mL)
3. extractionfollowed by extraction with dichloromethane (2×200 mL)
4. washThe organic layer was washed with ammonium chloride solution (3×30 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo
8. customthe crude product was crystallized from ethyl acetate and hexanes

ORD record

ord-6bbaa29ce107468aa5885d6c5c494a23

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933236B2