Sodium Carbonate → 6-Fluoro-2,3'-bipyridine

HRID 1812170Notes

Reaction equation

HRID 1812170 reaction equation
Cl[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[N:3]=1.[N:9]1[CH:14]=[CH:13][CH:12]=[C:11](B(O)O)[CH:10]=1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:8][C:4]1[N:3]=[C:2]([C:11]2[CH:10]=[N:9][CH:14]=[CH:13][CH:12]=2)[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 6394372-Chloro-6-fluoropyridineHCID 27343783-Pyridinylboronic acid

Product 1

HCID 463158166-Fluoro-2,3'-bipyridineYield 100.9%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

A mixture of 2-chloro-6-fluoro-pyridine (0.436 mL, 3.31 mmol) (Oakwood,), 3-pyridylboronic acid (448 mg, 3.65 mmol) (Combi-Blocks Inc.), and tetrakis(triphenylphosphine)palladium (0) (77 mg, 0.066 mmol) (Strem Chemicals) was purged with argon and dioxane (10 mL) and a 1 M solution of sodium carbonate (4.97 mL, 4.97 mmol) were added. The mixture was heated in a microwave at 110° C. for 30 min. The cooled reaction mixture was treated with 1 N NaOH and extracted with EtOAc (30 mL), washed with brine and dried over MgSO4, filtered and concentrated. Purification on the ISCO (12 g column, 70-100% EtOAc in hexanes) gave 6-fluoro-2,3′-bipyridine (581 mg, 3.34 mmol, 99% yield) as a pale yellow crystalline solid. m/z (ESI, +ve ion) 175.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 9.20 (1H, d, J=1.6 Hz); 8.67 (1H, d, J=3.9 Hz); 8.34 (1H, d, J=8.0 Hz); 7.90 (1H, q, J=8.0 Hz); 7.67 (1H, dd, J=7.5, 2.4 Hz); 7.42 (1H, dd, J=7.9, 4.8 Hz); 6.94 (1H, dd, J=8.0, 2.9 Hz).

Workup

  1. customwas purged with argon and dioxane (10 mL)
  2. customThe cooled reaction mixture
  3. extractionextracted with EtOAc (30 mL)
  4. washwashed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification on the ISCO (12 g column, 70-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c23cc2d9d11e408e958fc6428ee2f20e
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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