Ethyl Acetate → 5-Bromo-2-fluoro-3-phenylpyridine

HRID 1958462Notes

Reaction equation

HRID 1958462 reaction equation
[Br:1][C:2]1[CH:3]=[C:4](B(O)O)[C:5]([F:8])=[N:6][CH:7]=1.I[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.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>[Br:1][C:2]1[CH:3]=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:5]([F:8])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 11575IodobenzeneHCID 27832425-Bromo-2-fluoropyridine-3-boronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 120330125-Bromo-2-fluoro-3-phenylpyridineYield 49.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 5-bromo-2-fluoropyridin-3-ylboronic acid (620 mg, 2.82 mmol) and 1-iodobenzene (292 μL, 2.6 mmol) in 1,4-dioxane (50 μL) was degassed via nitrogen bubble for 15 mins. Then the mixture was added Pd(PPh3)4 (150 mg, 0.13 mmol) and aqueous Na2CO3 (24 μL, 5.7 mmol) and heated to 90° C. for 30 mins. The reaction was cooled to room temperature and poured into ethyl acetate (50 mL). The mixture was extracted with ethyl acetate, dried over Na2SO4, filtered and concentrated. The residue was purified via a flash column using 10% ethyl acetate in hexanes as an eluent. The product containing fractions were concentrated to give 5-bromo-2-fluoro-3-phenylpyridine (2.2) (326 mg, 49.8% yield).

Workup

  1. custombubble for 15 mins
  2. temperatureThe reaction was cooled to room temperature
  3. extractionThe mixture was extracted with ethyl acetate
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via a flash column
  8. additionThe product containing fractions
  9. concentrationwere concentrated

Sources & evidence

ORD record
ord-bf0ed854d16a4fe1b02e84db0e45d5ff
Source dataset
uspto-grants-2013_04
Patent number
US08410128B2

Reaction notes

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