反应详情

温度

80 °C

Acetic anhydride (10.0 mL, 106 mmol) was added dropwise to a benzene solution (110 mL) containing 5-chloro-2-methylaniline (5.0 g, 35.3 mmol) and potassium acetate (3.8 g, 38.7 mmol) at room temperature. After 10 minutes the reaction mixture, which had formed a thick white suspension, was heated to 80° C. Tert-butyl nitrite (6.99 mL, 90%, 53.0 mmol) was added over 20 minutes. The reaction mixture was kept at 80° C. overnight. The reaction was then cooled to room temperature and concentrated. The residue was dissolved in MeOH and stirred for 10 minutes. The solution was concentrated and to the residue was added MeOH (175 mL), THF (30 mL), water (60 mL) and lithium hydroxide monohydrate (8 g, 195 mmol). The solution was then stirred overnight at room temperature. The solution was then concentrated and the residue partitioned between EtOAc and 0.5 M NaOH aq. The aqueous phase was extracted twice with EtOAc. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give the indicated product. The material was used in Step B without further purification. 1H NMR (400 MHz, CH3CN-d3): δ 11.20 (broad s, 1H); 8.01 (s, 1H); 7.75-7.70 (m, 1H); 7.60 (s, 1H); 7.13 (dd, J=8.6, 1.7 Hz, 1H). m/z=153.0 (M+H).

1. customwhich had formed a thick white suspension
2. waitThe reaction mixture was kept at 80° C. overnight
3. temperatureThe reaction was then cooled to room temperature
4. concentrationconcentrated
5. dissolutionThe residue was dissolved in MeOH
6. concentrationThe solution was concentrated and to the residue
7. stirringThe solution was then stirred overnight at room temperature
8. concentrationThe solution was then concentrated
9. customthe residue partitioned between EtOAc and 0.5 M NaOH aq. The aqueous phase
10. extractionwas extracted twice with EtOAc
11. washThe combined organics were washed with brine
12. dry with materialdried over MgSO4
13. filtrationfiltered
14. concentrationconcentrated
15. customto give the indicated product
16. customThe material was used in Step B without further purification