Cesium fluoride → Methyl 2-fluoro-6-(pyrimidin-2-yl)benzoate

HRID 2174683Notes

Reaction equation

HRID 2174683 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8](I)[C:3]=1[C:4]([O:6][CH3:7])=[O:5].C([Sn](CCCC)(CCCC)[C:18]1[N:23]=[CH:22][CH:21]=[CH:20][N:19]=1)CCC.[F-].[Cs+]>CN(C=O)C.CCOC(C)=O.[Cu](I)I.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>[CH3:7][O:6][C:4](=[O:5])[C:3]1[C:8]([C:18]2[N:23]=[CH:22][CH:21]=[CH:20][N:19]=2)=[CH:9][CH:10]=[CH:11][C:2]=1[F:1]

Participants

8

Reactant 3

HCID 25953Cesium fluorideHCID 27632512-(Tributylstannyl)pyrimidineHCID 12192164Methyl 2-fluoro-6-iodobenzoate

Product 1

HCID 67086836Methyl 2-fluoro-6-(pyrimidin-2-yl)benzoate

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

Methyl 2-fluoro-6-iodobenzoate (17 g, 61 mmol, 1 eq.) and 2-(tributylstannyl)pyrimidine (26.7 g, 72 mmol, 1.2 eq.) were dissolved in 120 ml of dry DMF under nitrogen atmosphere. Cesium fluoride (18.1 g, 119 mmol, 2 eq., highly hygroscopic) was added and nitrogen was bubbled into the suspension for 5 minutes. While bubbling, Copper iodide (1.1 g, 5.77 mmol 0.1 eq.) and tetrakis(triphenylphosphine)palladium(0) (6.9 g, 5.97 mmol, 0.1 eq) were added. The mixture was then heated at 115° C. for 45 minutes. After that, it was allowed to cool to room temperature, diluted with a large volume of AcOEt and filtered over celite. The resulting liquid phase was washed thoroughly with a saturated aqueous solution of ammonium chloride to remove DMF, dried with sodium sulphate, filtered and evaporated to dryness.

Workup

  1. customnitrogen was bubbled into the suspension for 5 minutes
  2. customWhile bubbling
  3. temperatureto cool to room temperature
  4. filtrationfiltered over celite
  5. washThe resulting liquid phase was washed thoroughly with a saturated aqueous solution of ammonium chloride
  6. customto remove DMF
  7. dry with materialdried with sodium sulphate
  8. filtrationfiltered
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-5c8637e7c9444408bc56820010b98003
Source dataset
uspto-grants-2015_06
Patent number
US09062033B2

Reaction notes

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