Tetrahydrofuran → Methyl 2,4-dichloro-5-(5-fluoropyridin-2-yl)benzoate

HRID 522141Notes

Reaction equation

HRID 522141 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[C:9](B2OC(C)(C)C(C)(C)O2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C1COCC1.Br[C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.O>[Cl:1][C:2]1[CH:11]=[C:10]([Cl:12])[C:9]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 27831712-Bromo-5-fluoropyridineHCID 68413491Methyl 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate

Product 1

HCID 118497070Methyl 2,4-dichloro-5-(5-fluoropyridin-2-yl)benzoateYield 67%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

To the solution of methyl 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate in anhydrous THF (Preparation 45, 10 mL, 1.61 g, 4.88 mmol) was added 2-bromo-5-fluoropyridine (856 mg, 4.88 mmol), sodium carbonate (1.55 g, 14.59 mmol) and water (2 mL). The reaction was degassed with nitrogen for 15 minutes followed by the addition of Pd(PPh3)4 (280 mg, 0.244 mmol) with further degassing for 5 minutes. The reaction was heated to reflux under a nitrogen atmosphere for 2 hours. The reaction was concentrated in vacuo and the residue partitioned between EtOAc (35 mL) and water (35 mL). The organic layer was dried over magnesium sulphate and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting with 5-20% EtOAc in heptanes to afford the title compound as a white solid (1 g, 67%).

Workup

  1. customThe reaction was degassed with nitrogen for 15 minutes
  2. customwith further degassing for 5 minutes
  3. temperatureThe reaction was heated
  4. temperatureto reflux under a nitrogen atmosphere for 2 hours
  5. concentrationThe reaction was concentrated in vacuo
  6. customthe residue partitioned between EtOAc (35 mL) and water (35 mL)
  7. dry with materialThe organic layer was dried over magnesium sulphate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel column chromatography
  10. washeluting with 5-20% EtOAc in heptanes

Sources & evidence

ORD record
ord-3411ffdbec13478395c69071caf461a8
Source dataset
uspto-grants-2016_05
Patent number
US09328096B2

Reaction notes

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