Реакция #2286318

Уравнение реакции

[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile

[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile

ethyl acetate

→

acetic acid

Выход 13.0%

[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid

Выход 13.0%

Растворители

hydrochloric acid

Условия реакции

Обработка

1. 1
   Температураwas heated
2. 2
   Температураto reflux for 24 h
3. 3
   Промывкаwashed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL)
4. 4
   Экстракцияextracted with ethyl acetate (50 mL)
5. 5
   Сушкаdried over magnesium sulfate
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated under vacuum
8. 8
   ДругоеThe resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid)
9. 9
   ДругоеThe desired fractions were collected
10. 10
    Концентрированиеconcentrated
11. 11
    Другоеfreeze dried
12. 12
    ДругоеThe resulting solid was purified by flash chromatography
13. 13
    Промывкаeluted with 10% methanol in methylene chloride
14. 14
    ДругоеThe desired fractions were collected
15. 15
    Концентрированиеconcentrated under vacuum
16. 16
    Другоеto afford a solid which
17. 17
    Другоеwas dried under high vacuum

Методика

A mixture of [3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile (55) (assume 0.180 mmol) in concentrated hydrochloric acid (4 mL) was heated to reflux for 24 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (75 mL) and washed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL). The water layers were combined and extracted with ethyl acetate (50 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under vacuum. The resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid). The desired fractions were collected, concentrated and freeze dried. The resulting solid was purified by flash chromatography using silica gel eluted with 10% methanol in methylene chloride. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid (56) (8.6 mg, 13% for 2 steps) as a white solid; EI(+)-HRMS m/z calcd for C16H16Cl2N2O3 (M+H)+ 355.0611, found 355.0611. MW=355.2235, Exact Mass=354.0538

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