反应详情

4-Chloro-5-fluoro-1,2-phenylenediamine (12a, 3.212 g, 20 mmol) was dissolved in 40 mL of MeOH and then added dropwise to a stirred solution of 4.4 mL of 5M BrCN/MeCN in 40 mL of H2O over 30 min. After the addition, stirring was continued at room temperature for 3 hr. The reaction mixture was concentrated to ~40 mL and then was washed with EtOAc (100 mL). The EtOAc phase was extracted with H2O (60 mL). The combined H2O phase was neutralized with sat. NaHCO3 solution to ~pH 8 and the resulting suspension was extracted with EtOAc (200 mL). The EtOAc phase was washed with a mixture of sat. NaHCO3 /sat. NaCl solution (20 mL/180 mL), dried (Na2SO4), and evaporated. The residue was coevaporated with CHCl3 (20 mL×2) and then was suspended in 50 mL of CHCl3. The suspension was filtered to give 3.340 g of 12b as a grey solid. The filtrate was evaporated and coevaporated with CHCl3. The resulting solid was again suspended in a small amount of CHCl3 and the suspension was filtered to give an additional 0.235 g of 12b. The total yield of 12b was 3.575 g (96%). This product showed a single spot on TLC. MP: 194°-196° C. MS: (El) m/e 185.0156 (100%, M+ =185.0156). 1H NMR (DMSO-d6): d 10.85, (br s, 1, 1-NH), 7.16 (d, 1, 4-H, 4JF-H =7.0 Hz), 7.06 (d, 1, 7-H, 3JF-H =10.0 Hz), 6.43 (br s, 2, 2-NH2). Anal. Calcd. for C7H5ClFN3 ; C, 45.30; H, 2.72; N, 22.64. Found: C, 45.14; H, 2.67; N, 22.44.

1. additionAfter the addition
2. concentrationThe reaction mixture was concentrated to ~40 mL
3. washwas washed with EtOAc (100 mL)
4. extractionThe EtOAc phase was extracted with H2O (60 mL)
5. extractionthe resulting suspension was extracted with EtOAc (200 mL)
6. washThe EtOAc phase was washed with a mixture of sat. NaHCO3 /
7. dry with materialNaCl solution (20 mL/180 mL), dried (Na2SO4)
8. customevaporated
9. filtrationThe suspension was filtered