Acetone, oxime → HCID 86599612, compound

HRID 2102419Notes

Reaction equation

HRID 2102419 reaction equation
[CH3:1][C:2](=[N:4][OH:5])[CH3:3].CC([O-])(C)C.[K+].[CH3:12][O:13][C:14]([C:16]1[C:21]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[F:29])=[C:20]([F:30])[C:19](Cl)=[C:18]([C:32](=[O:34])[CH3:33])[N:17]=1)=[O:15]>C1COCC1>[CH3:12][O:13][C:14]([C:16]1[C:21]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[F:29])=[C:20]([F:30])[C:19]([O:5][N:4]=[C:2]([CH3:3])[CH3:1])=[C:18]([C:32](=[O:34])[CH3:33])[N:17]=1)=[O:15]

Participants

5

Reactant 3

HCID 67180Acetone, oximeHCID 23665647Potassium tert-butoxideHCID 66999313HCID 66999313, compound

Product 1

HCID 86599612HCID 86599612, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of acetone oxime (2.20 equivalents) at room temperature is added t-BuOK (2.20 equivalents, 1.0 M solution in THF). After stirring for 30 minutes room temperature, the reaction mixture is cooled to 0° C. A solution 6-acetyl-5-chloro-4-fluoro-3-(2-fluorophenylamino)-pyridine-2-carboxylic acid methyl ester (1.00 equivalent) in THF is added. After stirring for 1 hour at 0-5° C., the reaction mixture is quenched with saturated aqueous NH4Cl and diluted with EtOAc. The organic layer is washed with brine, dried over MgSO4, concentrated in vacuo to give 6-acetyl-4-fluoro-3-(2-fluorophenylamino)-5-isopropylideneaminooxy-pyridine-2-carboxylic acid methyl ester that is used directly. A mixture of 6-acetyl-4-fluoro-3-(2-fluorophenylamino)-5-isopropylideneaminooxy-pyridine-2-carboxylic acid methyl ester in 5% aqueous MeOH is refluxed with stirring for 1 hour. The reaction mixture is diluted with EtOAc and washed with water. The organic layer is dried over MgSO4, filtered, and concentrated in vacuo to give the crude material that is purified by flash column chromatography to afford the desired product.

Workup

  1. temperaturethe reaction mixture is cooled to 0° C
  2. stirringAfter stirring for 1 hour at 0-5° C.
  3. customthe reaction mixture is quenched with saturated aqueous NH4Cl
  4. additiondiluted with EtOAc
  5. washThe organic layer is washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-4af073fe2d874bda8a5377f31cabb168
Source dataset
uspto-grants-2009_08
Patent number
US07576072B2

Reaction notes

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