Imidazole → 3-(1H-Imidazol-1-yl)pyridine

HRID 1913374Notes

Reaction equation

HRID 1913374 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].F[C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[N:1]1([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 677943-FluoropyridineHCID 516892Sodium Bicarbonate

Product 1

HCID 47306953-(1H-Imidazol-1-yl)pyridineYield 59%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of imidazole (420 mg, 6.3 mmol) in DMF (6 mL) was added NaH (60% dispersion in mineral oil, 250 mg, 6.3 mmol) and the resultant solution was stirred at room temperature for 30 min under argon. To the solution was added a solution of 3-fluoropyridine (183 μL, 2.1 mmol) in DMF (2 mL) and the resultant solution was heated to 100° C. and stirred overnight. The solution was cooled to it, poured into aqueous saturated sodium bicarbonate (50 mL), extracted with ethyl acetate (3×50 mL), washed with brine, dried (Na2SO4), filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH3OH/CH2Cl2, 5/95, Rf=0.12) to afford the title compound 63 (176 mg, 59% yield) as a yellow oil: 1H NMR (CDCl3) δ 8.75 (m, 1H), 8.63 (m, 1H), 7.87 (s, 1H), 7.73 (m, 1H), 7.44 (m, 1H), 7.30 (s, 1H), 7.26 (s, 1H); LRMS (ESI) m/z calcd for C8H8N3 [M+H]+ 146. found 146; HRMS (ESI) m/z calcd for C8H8N3 [M+H]+ 146.0718. found 146.0730; HPLC>99% (tR=7.18 min, 55 (A):45 (B): 0.032 (C); 5.06 min, 55 (A):45 (B): 0.1 (C).

Workup

  1. temperatureThe solution was cooled to it
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washwashed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent was removed in vacuo
  7. customThe crude material was chromatographed on silica gel (CH3OH/CH2Cl2, 5/95, Rf=0.12)

Sources & evidence

ORD record
ord-5ebbc173fcd4496a85fc3904eda49c6e
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

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