1,4-Dioxane → HCID 86695924, compound

HRID 2369521Notes

Reaction equation

HRID 2369521 reaction equation
Cl[C:2]1[C:7]([C:8]([O-:10])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=1[F:11].[Cl:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[C:15]([F:22])[CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOC[CH2:32]1>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:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[C:7]([C:8]([O:10][CH3:32])=[O:9])=[CH:6][N:5]=[CH:4][C:3]=2[F:11])=[C:15]([F:22])[CH:14]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86335698HCID 86335698, compound

Product 1

HCID 86695924HCID 86695924, compoundYield 50%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a solution of 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) and potassium phosphate, dibasic (2.205 g, 12.66 mmol). To this mixture, PdCl2(dppf) (0.371 g, 0.506 mmol) was added and the solution purged with N2 for 10 min then heated to 80° C. for 12 h. The mixture was cooled to room temperature and water (25 mL) was added. The solution was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (25 mL) and concentrated under reduced pressure to afford the residue which was purified by silica gel column using a gradient of ethyl acetate in hexanes to afford methyl 4-(4-chloro-2-fluorophenyl)-5-fluoronicotinate (900 mg, 3.17 mmol, 50% yield) as a yellow solid. LCMS (ESI) m/e 284.0 [(M+H)+, calcd for C13H9ClF2NO2 284.0]; LC/MS retention time (Method F): tR=1.01 min.

Workup

  1. customthe solution purged with N2 for 10 min
  2. temperatureThe mixture was cooled to room temperature
  3. additionwater (25 mL) was added
  4. extractionThe solution was extracted with ethyl acetate (3×25 mL)
  5. washThe combined organic layers were washed with brine (25 mL)
  6. concentrationconcentrated under reduced pressure
  7. customto afford the residue which
  8. customwas purified by silica gel column

Sources & evidence

ORD record
ord-32a1a72a9d02492fbebc918bc389e83e
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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