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温度

0 °C

2-Amino-3-nitrophenol 1b1 (5 g; 32.4 mmol) was dissolved in H2O (29.5 mL) and 1,4-dioxane (14.7 mL). The mixture was heated to reflux and hydrobromic acid (48%; 16.7 mL; 147 mmol) was added dropwise over a period of 20 min. Upon completion of the addition, the reflux was maintained an additional 15 min. The reaction was cooled to 0° C. (ice bath), and sodium nitrite (2.23 g; 32.3 mmol) in H2O (20 mL) was added over a period of 30 min. The stirring was continued for 15 min. at 0° C., the mixture transferred to a jacketed dropping funnel (0° C.) and added dropwise to a stirred mixture of Cu(I)Br (5.34 g; 37.2 mmol) in H2O (29.5 mL) and HBr (48%; 16.7 mL; 147 mmol) at 0° C. The reaction was stirred for 15 min. at 0° C., warmed to 60° C., stirred for an additional 15 min., cooled to room temperature, and left to stir overnight. The reaction mixture was transferred to a separatory funnel and extracted with ether (3×150 mL). The organic layers were combined, washed with brine (1×), dried (Na2SO4), filtered and concentrated to afford the crude product (7.99 g) as a red-brown oil. The crude material was purified by flash column chromatography (1:25 ultra pure silica gel, 230-400 mesh, 40-60 mm, 60 angstroms; CH2Cl2 as the solvent) to afford pure 2-bromo-3-nitrophenol 1b2 (45%; 3.16 g) as an orange-brown solid. MS 217.8 (MH)−. Homogeneity by HPLC (TFA)@220 nm: 97%.

1. temperatureThe mixture was heated
2. temperatureto reflux
3. additionUpon completion of the addition
4. temperaturethe reflux was maintained an additional 15 min
5. additionwas added over a period of 30 min
6. customthe mixture transferred to a jacketed dropping funnel
7. temperaturewarmed to 60° C.
8. stirringstirred for an additional 15 min.
9. temperaturecooled to room temperature
10. waitleft
11. stirringto stir overnight
12. customThe reaction mixture was transferred to a separatory funnel
13. extractionextracted with ether (3×150 mL)
14. washwashed with brine (1×)
15. dry with materialdried (Na2SO4)
16. filtrationfiltered
17. concentrationconcentrated
18. customto afford the crude product (7.99 g) as a red-brown oil
19. customThe crude material was purified by flash column chromatography (1:25 ultra pure silica gel, 230-400 mesh, 40-60 mm, 60 angstroms