Hydrochloric Acid → 6-(3-fluoro-4-methylphenyl)-4-hydroxymethyl-2-isobutyl-2H-pyridazin-3-one

HRID 1348693Notes

Reaction equation

HRID 1348693 reaction equation
[C:1]([C:4]1[C:5](=[O:22])[N:6]([CH2:18][CH:19]([CH3:21])[CH3:20])[N:7]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([F:17])[CH:11]=2)[CH:9]=1)(O)=[O:2].C(N(CC)CC)C.C(Cl)(=O)OCC.[BH4-].[Na+].Cl>C1COCC1.O>[F:17][C:12]1[CH:11]=[C:10]([C:8]2[CH:9]=[C:4]([CH2:1][OH:2])[C:5](=[O:22])[N:6]([CH2:18][CH:19]([CH3:21])[CH3:20])[N:7]=2)[CH:15]=[CH:14][C:13]=1[CH3:16]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 219914814-carboxy-6-(3-fluoro-4-methylphenyl)-2-isobutyl-2H-pyridazin-3-one

Product 1

HCID 219914146-(3-fluoro-4-methylphenyl)-4-hydroxymethyl-2-isobutyl-2H-pyridazin-3-oneYield 25%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 4-carboxy-6-(3-fluoro-4-methyl-phenyl)-2-isobutyl-2H-pyridazin-3-one (4.53 g, 14.9 mmol) in THF (40 mL) was added triethylamine (1.66 g, 16.4 mmol). To the ice-cooled mixture was added dropwise a solution of ethyl chlorocarbonate (1.78 g, 16.4 mmol) in THF (5 mL), and the mixture was stirred for 30 minutes. Triethylamine hydrochloride was filtered off. An ice-cold solution of sodium borohydride (564 mg, 14.9 mmol) in water (1 mL) was added to the filtrate, and then, the mixture was stirred at room temperature for 10 minutes. Thereafter, 2 mol/L hydrochloric acid was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel [silica gel 300 g, chloroform/methanol (100/1→50/1)) to yield the title compound as a colorless crystalline powder (1.08 g, 25.0%).

Workup

  1. filtrationTriethylamine hydrochloride was filtered off
  2. stirringthe mixture was stirred at room temperature for 10 minutes
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel [silica gel 300 g, chloroform/methanol (100/1→50/1))

Sources & evidence

ORD record
ord-0f15c48f6aff4b9d953341cf80f1e937
Source dataset
uspto-grants-2007_05
Patent number
US07211577B2

Reaction notes

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