Reaction #2286314

Reaction equation

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

Yield 51.0%

Solvents

water

water

acetic acid

Conditions

Workup

1. 1
   TemperatureThe reaction was cooled to room temperature
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   TemperatureThe reaction was heated to 100° C. where vigorous gas evolution
4. 4
   Temperaturethe reaction was cooled to room temperature
5. 5
   workup.ADDITIONpoured onto ice water (100 mL)
6. 6
   Extractionwas extracted with ether (3×75 mL)
7. 7
   WashThe ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL)
8. 8
   OtherThe organic layer was separated
9. 9
   Dryingdried with magnesium sulfate
10. 10
    Filtrationfiltered
11. 11
    Concentrationconcentrated under vacuum
12. 12
    OtherThe resulting solid was purified by flash chromatography
13. 13
    Washeluted with a gradient of 4:1 to 2:1 ethyl acetate
14. 14
    OtherThe desired fractions were collected
15. 15
    Concentrationconcentrated under vacuum
16. 16
    Otherto afford a solid which
17. 17
    Otherwas dried under high vacuum

Procedure

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

Source