HCID 86599612, compound → HCID 69005301, compound

HRID 2102420Notes

Reaction equation

HRID 2102420 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:10]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[F:18])=[C:9]([F:19])[C:8]([O:20][N:21]=[C:22](C)[CH3:23])=[C:7](C(=O)C)[N:6]=1)=[O:4]>CO.CCOC(C)=O>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]2[C:22]([CH3:23])=[N:21][O:20][C:8]2=[C:9]([F:19])[C:10]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])=[O:4]

Participants

4

Reactant 1

HCID 86599612HCID 86599612, compound

Product 1

HCID 69005301HCID 69005301, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

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. temperatureis refluxed
  2. washwashed with water
  3. dry with materialThe organic layer is dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give the crude material that
  7. customis purified by flash column chromatography

Sources & evidence

ORD record
ord-57186ee7c2ab4fa6953729a71650a968
Source dataset
uspto-grants-2009_08
Patent number
US07576072B2

Reaction notes

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