Réaction #2286336

Équation de réaction

[3,5-dichloro-4-(6-chloro-5-isopropyl-pyridazin-3-ylsulfanyl)-phenyl]-acetic acid

[3,5-Dichloro-4-(6-chloro-5-isopropyl-pyridazin-3-ylsulfanyl)-phenyl]-acetic acid

sodium acetate

→

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

Rendement 47.8%

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

Rendement 47.8%

Solvants

acetic acid

Conditions de réaction

Traitement

1. 1
   ConcentrationAt this time, the reaction was concentrated in vacuo
2. 2
   Concentrationhexanes followed by concentration under vacuum
3. 3
   workup.ADDITIONThe resulting solid was diluted with water (100 mL)
4. 4
   workup.ADDITIONwas then treated with a 1N aqueous sodium hydroxide solution
5. 5
   ExtractionThis solution was extracted with ethyl acetate
6. 6
   ExtractionThis solution was then extracted with ethyl acetate (2×100 mL)
7. 7
   LavageThe organics were washed with a saturated aqueous sodium chloride solution (1×100 mL)
8. 8
   Séchagedried with magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated under vacuum

Mode opératoire

A mixture of [3,5-dichloro-4-(6-chloro-5-isopropyl-pyridazin-3-ylsulfanyl)-phenyl]-acetic acid (75) (90 mg, 0.23 mmol) and sodium acetate (66 mg, 0.80 mmol) in glacial acetic acid (2.5 mL) was heated to 100° C. for 7 h. At this time, the reaction was concentrated in vacuo. The residue was slurried three times in a 1:1 solution of methylene chloride:hexanes followed by concentration under vacuum. The resulting solid was diluted with water (100 mL) and was then treated with a 1N aqueous sodium hydroxide solution to adjust the pH between 10-11. This solution was extracted with ethyl acetate. The organics were discarded. The aqueous layer was then acidified to pH=2-3 with a 1N aqueous hydrochloric acid solution. This solution was then extracted with ethyl acetate (2×100 mL). The organics were washed with a saturated aqueous sodium chloride solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 70:30 hexanes/ethyl acetate with 2% glacial acetic acid) afforded [3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylsulfanyl)-phenyl]acetic acid (76) (41 mg, 17.5%) as a white solid; EI(+)-HRMS m/e calcd for C15H14Cl2N2O3S (M+H)+ 373.0175, found 373.0175. Exact Mass=372.0102; Molecular Weight=373.26

Source