Reaction #2286318

Reaction equation

[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

Yield 13.0%

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

Yield 13.0%

Solvents

hydrochloric acid

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureto reflux for 24 h
3. 3
   Washwashed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL)
4. 4
   Extractionextracted with ethyl acetate (50 mL)
5. 5
   Dryingdried over magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under vacuum
8. 8
   OtherThe resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid)
9. 9
   OtherThe desired fractions were collected
10. 10
    Concentrationconcentrated
11. 11
    Otherfreeze dried
12. 12
    OtherThe resulting solid was purified by flash chromatography
13. 13
    Washeluted with 10% methanol in methylene chloride
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 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

Source