Hydrochloric Acid → methyl (Z)-2-(difluoromethyl)-5-(3-hydroxy-1-oxo-2-propenyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate

HRID 256808Notes

Reaction equation

HRID 256808 reaction equation
[C:1]([C:4]1[C:5]([CH2:21][CH:22]([CH3:24])[CH3:23])=[C:6]([C:17]([O:19][CH3:20])=[O:18])[C:7]([CH:14]([F:16])[F:15])=[N:8][C:9]=1[C:10]([F:13])([F:12])[F:11])(=[O:3])[CH3:2].[CH:25](OC)=[O:26].C[O-].[Na+].Cl>CCOCC.CO.O.CC(C)=O.N1C=CC=CC=1>[F:15][CH:14]([F:16])[C:7]1[C:6]([C:17]([O:19][CH3:20])=[O:18])=[C:5]([CH2:21][CH:22]([CH3:24])[CH3:23])[C:4]([C:1](=[O:3])/[CH:2]=[CH:25]\[OH:26])=[C:9]([C:10]([F:12])([F:13])[F:11])[N:8]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 7865Methyl formateHCID 10942334Sodium MethoxideHCID 20098194Methyl 5-acetyl-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate

Product 1

HCID 86747352methyl (Z)-2-(difluoromethyl)-5-(3-hydroxy-1-oxo-2-propenyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylateYield 52.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 21978327HCID 21978327, compoundSolvent

Procedure

This example illustrates the preparation of Compound Numbers 23 and 24, an example of the acylation of a pyridine methyl ketone, followed by further derivation to compounds of the present invention. To methyl 5-acetyl-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (Compound No. 4, prepared as in Example A) (10.8 g, 30 mmol) in anhydrous ether (100 mL) were added methyl formate (3 g) and 25% sodium methoxide in methanol (10 g) (Aldrich), and the resulting mixture was stirred overnight. It was then poured into iced water, acidified with conc. HCl, and extracted with methylene chloride. The organic extract was washed with water and brine, dried (MgSO4), and conc. in vacuo. The residue was purified by flash chromatography with 20% ethyl acetate/cyclohexane to yield 6 g methyl (Z)-2-(difluoromethyl)-5-(3-hydroxy-1-oxo-2-propenyl)-4-(2-methylpropyl)-6-(trifluoromethyl)-3-pyridinecarboxylate (Compound No. 23) as a viscous red oil, a yield of 52.6%. nD25 1.4857.

Workup

  1. customthe preparation of Compound Numbers 23 and 24
  2. extractionextracted with methylene chloride
  3. extractionThe organic extract
  4. washwas washed with water and brine
  5. dry with materialdried (MgSO4)
  6. customThe residue was purified by flash chromatography with 20% ethyl acetate/cyclohexane

Sources & evidence

ORD record
ord-82d1dff2af09469b949922dac4b34280
Source dataset
uspto-grants-1993_11
Patent number
US05260262

Reaction notes

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