反应详情

To a solution of methyl 5-amino-2-bromo-4-methylbenzoate (4.86 g, 20 mmol) in hydrochloric acid (6N, 50 mL) was added sodium nitrite (1.38 g, 20 mmol) carefully at −5° C. After one hour, the obtained mixture was added to a boiling solution of copper(I) chloride (3.96 g, 40 mmol) in water (50 mL) dropwise and the resulting mixture was refluxed with stirring for 2 h. The mixture was cooled to rt and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography eluted with PE to give methyl 2-bromo-5-chloro-4-methylbenzoate (3.4 g, yield 64.4%). 1H NMR (400 MHz, DMSO-d6): δ 7.82 (s, 1H), 7.81 (s, 1H), 3.85 (s, 3H), 2.51 (s, 3H) ppm; MS: m/z=265.0 (M+1, ESI+).

1. temperaturethe resulting mixture was refluxed
2. extractionextracted with ethyl acetate (2×50 mL)
3. washThe combined organic layers were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by silica gel column chromatography
8. washeluted with PE