تفاعل #2286314

معادلة التفاعل

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

المردود 51.0%

المذيبات

water

water

acetic acid

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction was cooled to room temperature
2. 2
   workup.ADDITIONwas added dropwise
3. 3
   درجة الحرارةThe reaction was heated to 100° C. where vigorous gas evolution
4. 4
   درجة الحرارةthe reaction was cooled to room temperature
5. 5
   workup.ADDITIONpoured onto ice water (100 mL)
6. 6
   استخلاصwas extracted with ether (3×75 mL)
7. 7
   غسيلThe ether layer was cautiously washed with a saturated aqueous sodium bicarbonate solution (150 mL)
8. 8
   أخرىThe organic layer was separated
9. 9
   تجفيفdried with magnesium sulfate
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated under vacuum
12. 12
    أخرىThe resulting solid was purified by flash chromatography
13. 13
    غسيلeluted with a gradient of 4:1 to 2:1 ethyl acetate
14. 14
    أخرىThe desired fractions were collected
15. 15
    تركيزconcentrated under vacuum
16. 16
    أخرىto afford a solid which
17. 17
    أخرىwas dried under high vacuum

الإجراء التجريبي

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

المصدر