Water → 1-[(difluoromethyl)sulfonyl]-3-(4,6-dimethoxy-1,3,5-triazin-2-yl)-5-fluoro-1,3-dihydro-2H-indol-2-one

Temperature

-10 °C

3-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-5-fluoro-1,3-dihydro-2H-indol-2-one (50 g) and 1-methyl-1H-imidazole (30.5 g) are introduced as initial charge in 430 ml of dichloromethane and cooled to −10° C. under nitrogen. With stirring, a solution of difluoromethanesulfonyl chloride (41.8 g) in 70 ml of dichloromethane is added dropwise at −15° C. to −5° C. over the course of 30 minutes, and the mixture is after-stirred for 4 hours at −15° C. to 0° C. 1-Methyl-1H-imidazole (2.7 g) and difluoromethanesulfonyl chloride (4.9 g) are added to the reaction mixture and stirred for 2 hours at 0° C. With ice cooling, 300 ml of water are added to the reaction mixture, the mixture is after-stirred for 30 minutes and the organic solvent is largely distilled off in vacuo. The residue is filtered, the solid product is washed twice with 150 ml of water and twice with 40 ml of acetonitrile and dried. This gives the title compound as a solid in an HPLC purity of 96% (63.9 g, 95% of theory). The UV absorption (maximum at 360 nm) verifies the N-sulfonylation of the product.

1. stirringthe mixture is after-stirred for 4 hours at −15° C. to 0° C
2. stirringstirred for 2 hours at 0° C
3. stirringthe mixture is after-stirred for 30 minutes
4. distillationthe organic solvent is largely distilled off in vacuo
5. filtrationThe residue is filtered
6. washthe solid product is washed twice with 150 ml of water and twice with 40 ml of acetonitrile
7. customdried

ORD record

ord-e1b8ea50f4744d488d7f3cb866d64c7a

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08969553B2