Potassium Carbonate → 6-[4-(3-hydroxypropyloxy)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone

HRID 2372712Notes

Reaction equation

HRID 2372712 reaction equation
Br[CH2:2][CH2:3][CH2:4][OH:5].[OH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]([CH3:20])[CH2:15][C:16](=[O:19])[NH:17][N:18]=2)=[CH:9][CH:8]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[OH:5][CH2:4][CH2:3][CH2:2][O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]([CH3:20])[CH2:15][C:16](=[O:19])[NH:17][N:18]=2)=[CH:9][CH:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 123083-Bromo-1-propanolHCID 1355424786-(4-Hydroxyphenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one

Product 1

HCID 156826426-[4-(3-hydroxypropyloxy)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 361 mg (1.62 mmol) of the THP-derivative of 3-bromo-1-propanol prepared above, 220 mg (1.08 mmol) of 6-(4-hydroxyphenyl)-5-methyl-4,5-dihydro-3(2H)-pyridazinone and 298 mg (2.15 mmol) of powdered anhydrous potassium carbonate in 3 ml of DMF is heated at 100° C. for 2 hr. After cooling the reaction mixture is diluted with 25 ml of water and extracted with EtOAc (3×25 ml). The combined organic extracts are washed once with water, dried (MgSO4), filtered, and the solvent removed under vacuum. The residue is taken up in 5 ml of methanol, about 200 mg of pyridinium p-toluenesulfonate added, and the mixture heated at 60° C. for 2 hr under N2. solvent is removed under vacuum and the residue is flash chromatographed on silica gel (95:5 CHCl3 :CH3OH) to give 252 mg of 6-[4-(3-hydroxypropyloxy)phenyl]-5-methyl-4,5-dihydro-3 (2H)-pyridazinone as a white solid. 1H-NMR (CDCl3): δ1.18 (d, 3H); 1.83 (t, 1H); 2.00 (quintuplet, 2H); 2.40 (d, 1H); 2.63 (d pair, 1H); 3.25 (m, 1H); 3.80 (m, 2H); 4.10 (t, 2H); 6.90 (d, 2H); 7.63 (d, 2H); 8.65 (s, 1H).

Workup

  1. temperatureAfter cooling the reaction mixture
  2. extractionextracted with EtOAc (3×25 ml)
  3. washThe combined organic extracts are washed once with water
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed under vacuum
  7. additionabout 200 mg of pyridinium p-toluenesulfonate added
  8. temperaturethe mixture heated at 60° C. for 2 hr under N2
  9. customsolvent is removed under vacuum
  10. customchromatographed on silica gel (95:5 CHCl3 :CH3OH)

Sources & evidence

ORD record
ord-e993bb86bf694a8e9db252e5e4efb44b
Source dataset
uspto-grants-1992_03
Patent number
US05100892

Reaction notes

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