Cesium carbonate → 4-(2-Fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester

HRID 421873Notes

Reaction equation

HRID 421873 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[NH2:9].C1(P(C2C=CC=CC=2)C2(P(C3C=CC=CC=3)C3C=CC=CC=3)CC=C3C(C=CC=C3)=C2C2C3C(=CC=CC=3)C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:62]([O:64][C:65]([C:67]1[C:72](Cl)=[C:71]([CH3:74])[C:70](=[O:75])[N:69]([CH3:76])[C:68]=1[CH3:77])=[O:66])[CH3:63]>C1(C)C=CC=CC=1.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:62]([O:64][C:65]([C:67]1[C:72]([NH:9][C:3]2[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=2[F:1])=[C:71]([CH3:74])[C:70](=[O:75])[N:69]([CH3:76])[C:68]=1[CH3:77])=[O:66])[CH3:63]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 679842-Fluoro-4-methylanilineHCID 666739724-Chloro-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl esterHCID 86595863(+/-)-2,2-Bis(diphenylphosphino)-1,1-binaphthyl

Product 1

HCID 666746314-(2-Fluoro-4-methylphenylamino)-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl esterYield 71%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

2-Fluoro-4-methylphenylamine (0.259 g, 2.07 mmol), palladium (II) acetate (0.046 g, 0.205 mmol), rac-2,2-bis(diphenylphosphino)-1,1′-binaphthyl (0.192 g, 0.308 mmol), and cesium carbonate (1.00 g, 3.08 mmol) were added to a solution of 4-chloro-1,2,5-trimethyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid ethyl ester (0.50 g, 2.05 mmol) in toluene (7 mL) in a sealed vial. After stirring 10 minutes, the mixture was heated to 80° C. After 24 hours, the reaction mixture was cooled to room temperature and diluted with EtOAc. The resulting precipitate was filtered and washed with EtOAc. The filtrate was diluted with EtOAc and washed with water. The aqueous layer was reextracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. Purification by flash column chromatography (20:1 methylene chloride/MeOH) gave 0.048 g (71%) desired product.

Workup

  1. waitAfter 24 hours
  2. temperaturethe reaction mixture was cooled to room temperature
  3. filtrationThe resulting precipitate was filtered
  4. washwashed with EtOAc
  5. additionThe filtrate was diluted with EtOAc
  6. washwashed with water
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customPurification by flash column chromatography (20:1 methylene chloride/MeOH)

Sources & evidence

ORD record
ord-1997d741b1ca4d1e9b346fcd8cdfdb47
Source dataset
uspto-grants-2012_01
Patent number
US08101611B2

Reaction notes

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