Reacción #2286314

Ecuación de reacción

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

Rendimiento 51.0%

Disolventes

water

water

acetic acid

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction was cooled to room temperature
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   TemperaturaThe reaction was heated to 100° C. where vigorous gas evolution
4. 4
   Temperaturathe reaction was cooled to room temperature
5. 5
   workup.ADDITIONpoured onto ice water (100 mL)
6. 6
   Extracciónwas extracted with ether (3×75 mL)
7. 7
   LavadoThe ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL)
8. 8
   OtroThe organic layer was separated
9. 9
   Secadodried with magnesium sulfate
10. 10
    Filtraciónfiltered
11. 11
    Concentraciónconcentrated under vacuum
12. 12
    OtroThe resulting solid was purified by flash chromatography
13. 13
    Lavadoeluted with a gradient of 4:1 to 2:1 ethyl acetate
14. 14
    OtroThe desired fractions were collected
15. 15
    Concentraciónconcentrated under vacuum
16. 16
    Otroto afford a solid which
17. 17
    Otrowas dried under high vacuum

Procedimiento

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

Fuente