Реакция #2286324

Уравнение реакции

hydrochloric acid

hydrochloric acid

(6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile

sodium acetate

→

6-(2,6-dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one

Выход 36.0%

6-(2,6-Dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one

Выход 36.0%

Растворители

acetic acid

ethyl acetate

acetic acid

Условия реакции

Обработка

1. 1
   Температураwas heated
2. 2
   Температураto reflux for 2.5 h
3. 3
   Температураheated
4. 4
   Температураto reflux for 18 h
5. 5
   Температураheated
6. 6
   Температураto reflux for an additional 24 h
7. 7
   ПромывкаThis solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
8. 8
   Сушкаa saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
9. 9
   Фильтрацияfiltered
10. 10
    Концентрированиеconcentrated under vacuum
11. 11
    workup.ADDITIONThe resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL)
12. 12
    Температураwas heated
13. 13
    Температураto reflux for 3 d
14. 14
    ТемператураAt this time, the reaction was cooled to 25° C.
15. 15
    workup.ADDITIONdiluted with ethyl acetate (150 mL)
16. 16
    ПромывкаThis solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
17. 17
    Сушкаa saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
18. 18
    Фильтрацияfiltered
19. 19
    Концентрированиеconcentrated under vacuum

Методика

A mixture of (6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (61) (332.8 mg, 0.61 mmol) and sodium acetate (103.8 mg, 1.26 mmol) in glacial acetic acid (2.7 mL) was heated to reflux for 2.5 h. The reaction was then treated with concentrated hydrochloric acid (2.0 mL) and heated to reflux for 18 h. At this time, the reaction was treated with more concentrated hydrochloric acid (6.0 mL) and additional glacial acetic acid (3.0 mL) and heated to reflux for an additional 24 h. The reaction was then cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. The resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL) and was heated to reflux for 3 d. At this time, the reaction was cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate) afforded 6-(2,6-dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one (62) (96.3 mg, 36%) as an off-white solid; LRMS for C15H15Br2ClN2O (M+H) at m/z=433. Molecular Weight=434.5606; Exact Mass=431.9240

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