Sodium Carbonate → HCID 69357950, compound

HRID 983409Notes

Reaction equation

HRID 983409 reaction equation
[F:1][C:2]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[C:11]([O-])(=O)[CH3:12].[K+].Br[C:17]1[C:22]([C:23]([OH:25])=[O:24])=[CH:21][N:20]=[CH:19][CH:18]=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:11]([O:25][C:23](=[O:24])[C:22]1[CH:17]=[C:18]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=2)[CH:19]=[N:20][CH:21]=1)[CH3:12]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 7360294-Bromo-2-fluorobenzonitrileHCID 27629154-Bromopyridine-3-carboxylic acid

Product 1

HCID 69357950HCID 69357950, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 2-fluoro-4-bromobenzonitrile in DMF is treated with potassium acetate, bispinacolatoboronate (1.1 equiv.) and catalytic PdCl2(dppf) and heated for 2 h at 80° C. The reaction mixture is cooled to room temperature and 4-bromonicotinic acid (1 equiv.) is added along with fresh catalyst and 2 M Na2CO3 and the resulting mixture is stirred at 80° C. for 18 h. Solvent is removed and the residue is treated with 4N HCl/dioxane in refluxing ethanol for 18 h. The reaction is evaporated and the residue in ethyl acetate is washed with NaHCO3 (aqueous), dried over MgSO4 and evaporated to give 5-(4-cyano-3-fluoro-phenyl)-nicotinic acid ethyl ester.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customSolvent is removed
  3. additionthe residue is treated with 4N HCl/dioxane
  4. temperaturein refluxing ethanol for 18 h
  5. customThe reaction is evaporated
  6. washthe residue in ethyl acetate is washed with NaHCO3 (aqueous)
  7. dry with materialdried over MgSO4
  8. customevaporated

Sources & evidence

ORD record
ord-b3f062b220f24a09895bc883525aa714
Source dataset
uspto-grants-2005_03
Patent number
US06864267B2

Reaction notes

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