1,2-Diamino-4,5-difluorobenzene → 5,6-difluoro-1H-1,3-benzodiazol-2-amine

To a stirred solution of 4.9 mL of 5M BrCN/MeCN in 50 mL of H2O, was added dropwise a solution of 3.515 g (24.389 mmole) of 10 in 50 mL of MeOH over 20 min. After the addition, stirring was continued at room temperature for 2 h. The reaction mixture was concentrated to ~50 mL arid was extracted with EtOAc (50 mL×3). The combined EtOAc solution was back washed with 100 mL of H2O and then discarded. The combined H2O phase was basified with sat. NaHCO3 solution (precipitation occurred) and was extracted again with EtOAc (70 mL×3). The EtOAc solution was dried (Na2SO4) and evaporated to dryness. The residue was suspended in 50 mL of CHCl3 and filtered. The yellowish solid was washed with portions of CHCl3 to give 3.40 g of 11. The filtrate and washings were evaporated to dryness and the procedure was repeated to give an additional 0.355 g of 11. The total yield of 11 was 3.755 g (91%). 1H NMR DMSO-d6) d 10.79 (br. s, 1, 1-NH). 7.06 (dd, 2, 4-H and 7-H, 3JF-H =11.0 Hz, 4JF-H =7.5 Hz), 6.30 (br. s, 2, 2-NH2).

1. additionAfter the addition
2. concentrationThe reaction mixture was concentrated to ~50 mL
3. extractionwas extracted with EtOAc (50 mL×3)
4. washThe combined EtOAc solution was back washed with 100 mL of H2O
5. extractionwas extracted again with EtOAc (70 mL×3)
6. dry with materialThe EtOAc solution was dried (Na2SO4)
7. customevaporated to dryness
8. filtrationfiltered
9. washThe yellowish solid was washed with portions of CHCl3

ORD record

ord-e8560434d9754da1a13a3a0a9a8a0b79

Source dataset

uspto-grants-1998_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05712255