反应详情

温度

3 °C

To a suspension of 5-methoxy-2-methylaniline (5.00 g, 36.4 mmol) in water (144 mL) at 10° C., was added conc. H2SO4 (56 mL), while maintaining internal temperature below 25° C. After 1 h at rt, the mixture was cooled to 3° C. and a solution of sodium nitrite (3.77 g, 54.7 mmol) in water (20 mL) was added dropwise over 30 min, keeping the internal temperature below 5° C. After 1 h at 3° C., the yellow heterogeneous mixture was poured into a 5° C. solution of CuBr (52.0 g, 364 mmol) in 48% aqueous HBr (260 mL). The dark mixture was heated at 60° C. for 2 h, allowed to cool to rt and extracted with Et2O (3×) (solid Na2S2O3 was added in the extraction process for partial decoloration). The combined organics were washed with 1 N NaOH (3×), 10% aq. Na2S2O3 and brine, dried (Na2SO4) and concentrated, affording the title compound as an orange liquid which was used without further purification in the next Step. 1H NMR (500 MHz, acetone-d6): δ 7.24 (d, 1H), 7.14 (d, 1H), 6.87 (dd, 1H), 3.80 (s, 3H), 2.31 (s, 3H).

1. temperaturewhile maintaining internal temperature below 25° C
2. customthe internal temperature below 5° C
3. waitAfter 1 h at 3° C.
4. temperatureThe dark mixture was heated at 60° C. for 2 h
5. temperatureto cool to rt
6. extractionextracted with Et2O (3×) (solid Na2S2O3
7. additionwas added in the extraction process for partial decoloration)
8. washThe combined organics were washed with 1 N NaOH (3×), 10% aq. Na2S2O3 and brine
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated