反应详情

To a cooled solution (−10° C.) of 2-amino-3-bromo-5-nitro-phenol (643 g, 2.76 mol) in EtOH (13 L) was added conc. H2SO4 (515 mL, 9.97 mol) over a period of 35 min at −10 to −2° C. The reaction mixture was allowed to warm to rt then heated to 50-55° C. followed by portion-wise addition of NaNO2 (671 g, 9.72 mol) over 30 min then heated at reflux for 3 h. After completion of reaction (by TLC), the mixture was concentrated to 3 L and cooled to 0° C. followed by the addition of chilled water (5 L) and extraction with EtOAc (3×6 L). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a semi-solid residue. The residue was treated with 25% ether-hexane mixture (6 L) and stirred for 1 h. The solid was filtered and washed with hexane (3 L) to obtain the desired product (505 g, 84%).

1. temperaturethen heated to 50-55° C.
2. temperaturethen heated
3. temperatureat reflux for 3 h
4. customAfter completion of reaction (by TLC)
5. concentrationthe mixture was concentrated to 3 L
6. temperaturecooled to 0° C.
7. additionfollowed by the addition of chilled water (5 L) and extraction with EtOAc (3×6 L)
8. washThe combined organic layers were washed with brine
9. dry with materialdried over anhydrous Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto give a semi-solid residue
13. filtrationThe solid was filtered
14. washwashed with hexane (3 L)