Potassium Carbonate → HCID 57516327, compound

HRID 1810980Notes

Reaction equation

HRID 1810980 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([F:10])[C:7](Cl)=[N:6][C:5]=1[Cl:12].[CH3:14]B1OB(C)OB(C)O1.C(=O)([O-])[O-].[K+].[K+]>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([CH3:14])=[N:6][C:5]=1[Cl:12]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 574072TrimethylboroxineHCID 2775354Methyl 2,6-dichloro-5-fluoronicotinate

Product 1

HCID 57516327HCID 57516327, compoundYield 45.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2,6-dichloro-5-fluoro-nicotinic acid methyl ester (1.00 g 4.46 mmol), trimethylboroxin (0.620 mL, 4.40 mmol), tetrakis(triphenylphosphine)palladium (0.500 g, 0.433 mmol) and potassium carbonate (1.50 g, 12.0 mmol) is heated at 110° C. overnight. The mixture is cooled to room temperature, diluted with water, and extracted with EtOAc. The combined organic phase is washed with water followed by brine, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is purified by flash silica gel chromatography using a gradient of 0-30% EtOAc/heptane to provide 0.410 g (45.1%) of 2-chloro-5-fluoro-6-methyl-nicotinic acid methyl ester as a solid.

Workup

  1. temperatureThe mixture is cooled to room temperature
  2. extractionextracted with EtOAc
  3. washThe combined organic phase is washed with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-f1eb6dc9169846bdbd3110794dea672e
Source dataset
uspto-grants-2013_01
Patent number
US08362249B2

Reaction notes

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