Ethyl Acetate → 3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxylic acid

HRID 2090530Notes

Reaction equation

HRID 2090530 reaction equation
I(O)(=O)(=O)=O.[F:6][C:7]1[N:11]([CH3:12])[N:10]=[C:9]([CH:13]([F:15])[F:14])[C:8]=1[CH:16]=[O:17].C(OCC)(=[O:20])C>C(#N)C.C1C=C[NH+]=CC=1.[O-][Cr](Cl)(=O)=O>[F:15][CH:13]([F:14])[C:9]1[C:8]([C:16]([OH:20])=[O:17])=[C:7]([F:6])[N:11]([CH3:12])[N:10]=1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 65185Metaperiodic acidHCID 19754735HCID 19754735, compound

Product 1

HCID 231925843-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxylic acidYield 83%

Reagents, catalysts & solvents 2

HCID 178418287HCID 178418287, compoundCatalystHCID 6342AcetonitrileSolvent2×

Procedure

A suspension of 79.7 g (350 mmol) of periodic acid in 640 ml of absolute acetonitrile was stirred for 30 min. At 0° C., 56.6 g (318 mmol) of 5-fluoro-1-methyl-3-difluoromethyl-1H-pyrazole-4-carbaldehyde (IV-1) and 1.4 g (6 mmol) of PCC dissolved in 130 ml of dry acetonitrile were added. The reaction mixture was subsequently stirred at room temperature for 2.5 hours. After 1600 ml of ethyl acetate had been added, the reaction mixture was washed in succession with saturated sodium chloride solution/water (1:1), saturated sodium metabisulphite solution and saturated sodium chloride solution. The organic phase was dried over sodium sulphate and concentrated to obtain 51.4 g (83% of theory) of 3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxylic acid (V-1) as a yellow solid.

Workup

  1. additionwere added
  2. stirringThe reaction mixture was subsequently stirred at room temperature for 2.5 hours
  3. washthe reaction mixture was washed in succession with saturated sodium chloride solution/water (1:1), saturated sodium metabisulphite solution and saturated sodium chloride solution
  4. dry with materialThe organic phase was dried over sodium sulphate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-d18dda3713dd4e1fa5f323c05b4df2af
Source dataset
uspto-grants-2013_05
Patent number
US08436191B2

Reaction notes

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