Sodium Acetate → HCID 15981274, compound

HRID 271207Notes

Reaction equation

HRID 271207 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:20][C:21]([OH:23])=[O:22])[CH:5]=[C:6]([Cl:19])[C:7]=1[S:8][C:9]1[N:10]=[N:11][C:12](Cl)=[C:13]([CH:15]([CH3:17])[CH3:16])[CH:14]=1.C([O-])(=[O:26])C.[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:20][C:21]([OH:23])=[O:22])[CH:5]=[C:6]([Cl:19])[C:7]=1[S:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:26])[NH:11][N:10]=1

Participants

4

Reactant 2

HCID 517045Sodium AcetateHCID 59834466HCID 59834466, compound

Product 1

HCID 15981274HCID 15981274, compoundYield 47.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
100 °C

Procedure

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

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. concentrationhexanes followed by concentration under vacuum
  3. additionThe resulting solid was diluted with water (100 mL)
  4. additionwas then treated with a 1N aqueous sodium hydroxide solution
  5. extractionThis solution was extracted with ethyl acetate
  6. extractionThis solution was then extracted with ethyl acetate (2×100 mL)
  7. washThe organics were washed with a saturated aqueous sodium chloride solution (1×100 mL)
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-fec180aa1ba4422aacd52e1030f623b0
Source dataset
uspto-grants-2008_11
Patent number
US07452882B2

Reaction notes

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