Sodium Carbonate → 2-(2-Fluoro-5-methylphenyl)pyridin-4-amine

HRID 1522555Notes

Reaction equation

HRID 1522555 reaction equation
Br[C:2]1[CH:7]=[C:6]([NH:8]C(=O)OC(C)(C)C)[CH:5]=[CH:4][N:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:16][C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 70155224-(Boc-amino)-2-bromopyridineHCID 103518842-Fluoro-5-methylbenzeneboronic acid

Product 1

HCID 674695782-(2-Fluoro-5-methylphenyl)pyridin-4-amineYield 532.9%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

Bis(triphenylphosphine)palladium chloride (0.406 g, 0.578 mmol), tert-butyl 2-bromopyridin-4-ylcarbamate (250 mg, 0.915 mmol), and 2-fluoro-5-methylphenylboronic acid (1.157 g, 7.51 mmol) and sodium carbonate (0.458 ml, 0.915 mmol) were combined in dioxane (10 mL) and heated to reflux for 5 hours. The reaction mixture was cooled, evaporated to remove most of the solvent, and partitioned between brine and EtOAc. The organic layer was separated and dried over Na2SO4, filtered, and concentrate under vacuum to give a residue which was purified by NH silica column chromatography eluting with Hex/EtOAc 1:1 to give a residue which was further purified by repeating the silica column chromatography using the same conditions to give the title compound (986 mg) as clear oil which solidified on standing. ESI-MS: m/z 203.1 (M+H).

Workup

  1. temperatureheated
  2. temperatureto reflux for 5 hours
  3. temperatureThe reaction mixture was cooled
  4. customevaporated
  5. customto remove most of the solvent
  6. custompartitioned between brine and EtOAc
  7. customThe organic layer was separated
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrate under vacuum
  11. customto give a residue which
  12. customwas purified by NH silica column chromatography
  13. washeluting with Hex/EtOAc 1:1
  14. customto give a residue which
  15. customwas further purified

Sources & evidence

ORD record
ord-eb2fdcfdfc37494581094e76156dd105
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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