Water → 4-Acetylamino-3-chloro-6-[2,4 dichloro-3-(1-fluoroethyl)phenyl]pyridine-2-carboxylic acid, methyl ester

HRID 1782622Notes

Reaction equation

HRID 1782622 reaction equation
[Cl:1][C:2]1[C:7]([CH:8]([F:10])[CH3:9])=[C:6]([Cl:11])[CH:5]=[CH:4][C:3]=1Br.[C:13]([NH:16][C:17]1[CH:22]=[C:21]([Sn](C)(C)C)[N:20]=[C:19]([C:27]([O:29][CH3:30])=[O:28])[C:18]=1[Cl:31])(=[O:15])[CH3:14].[F-].[Cs+].O>CN(C=O)C.[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:13]([NH:16][C:17]1[CH:22]=[C:21]([C:3]2[CH:4]=[CH:5][C:6]([Cl:11])=[C:7]([CH:8]([F:10])[CH3:9])[C:2]=2[Cl:1])[N:20]=[C:19]([C:27]([O:29][CH3:30])=[O:28])[C:18]=1[Cl:31])(=[O:15])[CH3:14]

Participants

8

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 226773084-Acetylamino-3-chloro-6-trimethylstannylpyridine-2-carboxylic acid methyl esterHCID 688089162,4 Dichloro-3-(1-fluoroethyl)-bromobenzene

Product 1

HCID 688086804-Acetylamino-3-chloro-6-[2,4 dichloro-3-(1-fluoroethyl)phenyl]pyridine-2-carboxylic acid, methyl ester

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 2,4 dichloro-3-(1-fluoroethyl)-bromobenzene (3.4 g, 12.5 mmol), 4-acetylamino-3-chloro-6-trimethylstannyl-pyridine-2-carboxylic acid, methyl ester (4.7 g, 12.5 mmol), copper iodide (0.4 g, 2.1 mmol), cesium fluoride (3.6 g, 25 mmol) and dichlorobis(triphenylphosphine)palladium (0.14 g, 2 mmol) in DMF (50 mL) was heated to 70° C. for 2 hours. Water (100 mL) was added the mixture extracted with ethyl acetate (2×100 mL). The combined extracts were washed with brine, dried (sodium sulfate) and concentrated. The residue was purified by chromatography (15%-30% ethyl acetate in hexanes) to give 4-acetylamino-3-chloro-6-[2,4 dichloro-3-(1-fluoroethyl)phenyl]pyridine-2-carboxylic acid, methyl ester which was used without further purification.

Workup

  1. extractionextracted with ethyl acetate (2×100 mL)
  2. washThe combined extracts were washed with brine
  3. dry with materialdried (sodium sulfate)
  4. concentrationconcentrated
  5. customThe residue was purified by chromatography (15%-30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b47ea4588ed34879940d3ad59339d2ce
Source dataset
uspto-grants-2009_03
Patent number
US07498468B2

Reaction notes

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