Hydrochloric Acid → HCID 68284964, compound

HRID 571615Notes

Reaction equation

HRID 571615 reaction equation
C([O:4][CH2:5][C:6]([CH2:8][S:9]([C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1)(=[O:11])=[O:10])=O)(=O)C.[CH3:19][NH:20][NH2:21].C(N([CH2:27][CH3:28])CC)C.[OH2:29].[OH-].[Li+].Cl.[CH2:33]1[CH2:37]O[CH2:35][CH2:34]1>O>[CH2:34]([C:33]1[CH:37]=[C:13]([CH3:12])[CH:14]=[C:15]([CH2:16][CH3:17])[C:18]=1[C:6]1[C:5](=[O:4])[N:20]([CH3:19])[N:21]=[C:28]([CH2:27][OH:29])[C:8]=1[S:9]([C:12]1[CH:13]=[CH:14][C:15]([CH3:18])=[CH:16][CH:17]=1)(=[O:10])=[O:11])[CH3:35]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6061MethylhydrazineHCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 168937Lithium hydroxide, monohydrateHCID 68284723HCID 68284723, compound

Product 1

HCID 68284964HCID 68284964, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

1-acetoxy-3-(4-methylphenylsulfonyl)acetone (17.5 g, 64.7 mmol) was dissolved in THF (60 ml), and ice-cooled. To the solution was slowly added methylhydrazine (2.98 g, 64.7 mmol) dropwise. After ice-bath was removed, the mixture was stirred at room temperature overnight. To the reaction solution was added triethylamine (10.8 ml, 77.5 mmol), and then a solution of (2,6-diethyl-4-methylphenyl)glyoxyl chloride (15.4 g, 64.7 mmol) in THF. (30 ml) was slowly added. The reaction mixture was stirred at room temperature for 3 hours, then stirred under reflux for 1.5 hours. After the reaction solution was cooled to room temperature, the reaction solution was diluted with water, and extracted with tert-butyl methyl ether. The organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, then saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in methanol (70 ml), and ice-cooled. To the solution was added lithium hydroxide monohydrate (8.14 g, 194 mmol), and stirred at 0° C. for 5 hours. To the reaction solution was added 2N hydrochloric acid (150 ml), concentrated under reduced pressure to remove methanol. The residue was extracted with ethyl acetate 2 times. The combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution, then saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give 2.58 g of 4-(2,6-diethyl-4-methylphenyl)-6-hydroxymethyl-5-(4-methylphenylsulfonyl)-2-methyl-3(2H)-pyridazinone (yield: 9%) as solid.

Workup

  1. temperatureice-cooled
  2. customAfter ice-bath was removed
  3. addition(30 ml) was slowly added
  4. stirringThe reaction mixture was stirred at room temperature for 3 hours
  5. stirringstirred
  6. temperatureunder reflux for 1.5 hours
  7. temperatureAfter the reaction solution was cooled to room temperature
  8. extractionextracted with tert-butyl methyl ether
  9. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate solution
  10. dry with materialsaturated brine, dried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe residue was dissolved in methanol (70 ml)
  13. temperatureice-cooled
  14. stirringstirred at 0° C. for 5 hours
  15. concentrationconcentrated under reduced pressure
  16. customto remove methanol
  17. extractionThe residue was extracted with ethyl acetate 2 times
  18. washThe combined organic layer was washed with saturated aqueous sodium hydrogen carbonate solution
  19. dry with materialsaturated brine, dried over anhydrous magnesium sulfate
  20. concentrationconcentrated under reduced pressure
  21. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-73a821b16383433fa32ab55da3172010
Source dataset
uspto-grants-2015_05
Patent number
US09029295B2

Reaction notes

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