Potassium Phosphate, Tribasic → HCID 86695924, compound

HRID 1398451Notes

Reaction equation

HRID 1398451 reaction equation
Cl[C:2]1[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[F:12].[Cl:13][C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[C:16]([F:23])[CH:15]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=2[F:12])=[C:16]([F:23])[CH:15]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 866959231454913-72-4

Product 1

HCID 86695924HCID 86695924, compoundYield 50.1%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of methyl 4-chloro-5-fluoronicotinate (1.2 g, 6.33 mmol) in 1,4-dioxane (12 mL) and water (0.5 mL) was added (4-chloro-2-fluorophenyl)boronic acid (1.214 g, 6.96 mmol). The mixture was then purged with nitrogen gas for 5 min. Potassium phosphate, dibasic (2.205 g, 12.66 mmol) and PdCl2(dppf) (0.371 g, 0.506 mmol) were added and again the mixture was purged with N2 for 5 min. The reaction mixture was heated to 80° C. for 12 h. After cooling, water was added to and the mixture was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using hexane and ethyl acetate to afford methyl 4-(4-chloro-2-fluorophenyl)-5-fluoronicotinate (900 mg, 3.17 mmol, 50% yield) as a yellow solid. LC/MS (ESI) m/e 284.0 [(M+H)+, calcd for C13H9ClF2NO2 284.02]; LC/MS retention time (method D): tR=1.01 min.

Workup

  1. customThe mixture was then purged with nitrogen gas for 5 min
  2. customagain the mixture was purged with N2 for 5 min
  3. temperatureAfter cooling
  4. additionwater was added to and the mixture
  5. extractionwas extracted with ethyl acetate (3×25 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-48aceb7ed8454f6fb9fec8decdc7b651
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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