Methanol → 6-(4-Hydroxyphenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one

HRID 344652Notes

Reaction equation

HRID 344652 reaction equation
[N:1]1[NH:2][C:3](=[O:7])[CH:4]=[CH:5][CH:6]=1.O.[C:9]1([CH3:19])[CH:14]=[CH:13][C:12](S(O)(=O)=O)=[CH:11][CH:10]=1.CO.[OH-].[Na+].[OH:24]P([O-])(O)=O.[K+]>O>[OH:24][C:12]1[CH:13]=[CH:14][C:9]([C:19]2[CH:5]([CH3:6])[CH2:4][C:3](=[O:7])[NH:2][N:1]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 887Methanol2×HCID 681533(2H)-PyridazinoneHCID 521998p-Toluenesulfonic acid monohydrateHCID 24942486NaOH KH2PO4

Product 1

HCID 1355424786-(4-Hydroxyphenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-oneYield 80%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 25 ml round-bottomed flask equipped with a stir bar and reflux condenser was charged with 0.10 g (0.49 mmol) of (-)-enriched-4,5-dihydro-6-(4'-hydroxyphenyl)-5-methyl-3(2H-pyridazinone (45% ee by chiral HPLC), 0.45 g (0.24 mmol) of p-toluenesulfonic acid monohydrate and methanol (15 ml). The solution was stirred under an atmosphere of nitrogen at reflux and epimerization of C-5 ° f the starting material was monitored by chiral HPLC (Cyclobond I, 75% pH 7 NaOH/KH2PO4 buffer, 25% methanol, 0.5 ml/min, lamba=280 nm). After 24 hrs, the starting material was nearly racemized. The solution was poured into water (30 ml) and extracted with EtOAc (3x35 ml). The combined EtOAc extracts were washed with saturated aqueous sodium chloride (50 ml), dried over anhydrous magnesium sulfate (5 g), filtered and concentrated in vacuo to provide 0.08 g (80%) of (±)-4,5-dihydro-6-(4'-hydroxyphenyl)-5-methyl-3(2H)-pyridazinone, m.p. 268°-273° C.; [α]D -9.8° (c 0.24, methanol); 2.5% optical purity.

Workup

  1. customA 25 ml round-bottomed flask equipped with a stir bar
  2. temperaturereflux condenser
  3. temperatureat reflux
  4. customepimerization of C-5 ° f
  5. extractionextracted with EtOAc (3x35 ml)
  6. washThe combined EtOAc extracts were washed with saturated aqueous sodium chloride (50 ml)
  7. dry with materialdried over anhydrous magnesium sulfate (5 g)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1f640b7e7ff54f2d97936b505be6062b
Source dataset
uspto-grants-1991_10
Patent number
US05053338

Reaction notes

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