반응 #2286314

반응 방정식

hydrogen bromide

sodium nitrite

6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one

6-(4-Amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one

sulfuric acid

→

6-(4-bromo-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one

수율 51.0%

용매

water

water

acetic acid

반응 조건

후처리

1. 1
   온도The reaction was cooled to room temperature
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   온도The reaction was heated to 100° C. where vigorous gas evolution
4. 4
   온도the reaction was cooled to room temperature
5. 5
   workup.ADDITIONpoured onto ice water (100 mL)
6. 6
   추출was extracted with ether (3×75 mL)
7. 7
   세척The ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL)
8. 8
   기타The organic layer was separated
9. 9
   건조dried with magnesium sulfate
10. 10
    여과filtered
11. 11
    농축concentrated under vacuum
12. 12
    기타The resulting solid was purified by flash chromatography
13. 13
    세척eluted with a gradient of 4:1 to 2:1 ethyl acetate
14. 14
    기타The desired fractions were collected
15. 15
    농축concentrated under vacuum
16. 16
    기타to afford a solid which
17. 17
    기타was dried under high vacuum

실험 절차

A solution of 6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one (46) (0.9 g, 2.88 mmol) in glacial acetic acid (16 mL) at room temperature was treated with concentrated sulfuric acid (4 mL). A solution of sodium nitrite (480 mg, 6.96 mmol) in water (5 mL) was added below the surface of the reaction slowly over 10 min. The reaction mixture was heated to 60° C. for 1 h. The reaction was cooled to room temperature and a mixture of copper(I) bromide (450 mg, 3.14 mmol) and 48% hydrogen bromide in water (2 mL, 17.68 mmol) was added dropwise. The reaction was heated to 100° C. where vigorous gas evolution occurred. After 1 h, the reaction was cooled to room temperature, poured onto ice water (100 mL) and was extracted with ether (3×75 mL). The ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL). The organic layer was separated, dried with magnesium sulfate, filtered and concentrated under vacuum. The resulting solid was purified by flash chromatography using silica gel eluted with a gradient of 4:1 to 2:1 ethyl acetate:hexanes. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 6-(4-bromo-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one (51) (553 mg, 51%) as an off-white solid; LRMS-ES(+) for C14H13BrCl2N2O (M+H) m/z=375. MW=376.0825, Exact Mass=373.9588

출처