反応 #2286314

反応方程式

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

収率 51.0%

溶媒

water

water

acetic acid

反応条件

後処理

1. 1
   温度The reaction was cooled to room temperature
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   温度The reaction was heated to 100° C. where vigorous gas evolution
4. 4
   温度the reaction was cooled to room temperature
5. 5
   workup.ADDITIONpoured onto ice water (100 mL)
6. 6
   抽出was extracted with ether (3×75 mL)
7. 7
   洗浄The ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL)
8. 8
   その他The organic layer was separated
9. 9
   乾燥dried with magnesium sulfate
10. 10
    ろ過filtered
11. 11
    濃縮concentrated under vacuum
12. 12
    その他The resulting solid was purified by flash chromatography
13. 13
    洗浄eluted with a gradient of 4:1 to 2:1 ethyl acetate
14. 14
    その他The desired fractions were collected
15. 15
    濃縮concentrated under vacuum
16. 16
    その他to afford a solid which
17. 17
    その他was dried under high vacuum

実験手順

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

出典