Nitrogen → 3-(4-Fluorophenyl)pyridine

HRID 341237Notes

Reaction equation

HRID 341237 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[F:8][C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1.N#N>COCCOC.C([O-])([O-])=O.[Na+].[Na+]>[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 947NitrogenHCID 122863-BromopyridineHCID 2856454-Fluorophenylboronic acid

Product 1

HCID 155443703-(4-Fluorophenyl)pyridineYield 109.6%

Reagents, catalysts & solvents 2

HCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

A solution of 3-bromopyridine (2.5 g, 15.8 mmol) and 4-fluorophenylboronic acid (2.8 g, 20.0 mmol) in DME (20 ml) and 2N Na2CO3 (aq, 20 ml) was deoxygenated by evacuation/refill with N2 (×2). PdCl2dppf (600 mg, 0.8 mmol) was added and the mixture was deoxygenated again (×3). The reaction was stirred and heated at 80° C. under N2 for 16 hours. After cooling to RT the mixture was partitioned between EtOAc/H2O. The aqueous layer was extracted with EtOAc (×2).The combined extracts were washed with brine (×1), dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica (10→40% EtOAc/Petrol) to give the title compound (3.0 g, oil). 1H NMR (400 MHz, CDCl3): 8.83 (1H, brs), 8.61 (1H, brs), 7.85 (1H, d), 7.54 (2H, dd), 7.39 (1H, brs), 7.18 (2H, t).

Workup

  1. customthe mixture was deoxygenated again (×3)
  2. temperatureAfter cooling to RT the mixture
  3. customwas partitioned between EtOAc/H2O
  4. extractionThe aqueous layer was extracted with EtOAc (×2).The combined extracts
  5. washwere washed with brine (×1)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by chromatography on silica (10→40% EtOAc/Petrol)

Sources & evidence

ORD record
ord-b8400f0d988f40b7a93acf334a4761ba
Source dataset
uspto-grants-2014_11
Patent number
US08895745B2

Reaction notes

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