2-Methylimidazole → 3-(2-Methyl-1H-imidazol-1-yl)pyridine

HRID 1913373Notes

Reaction equation

HRID 1913373 reaction equation
[CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[H-].[Na+].F[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH3:1][C:2]1[N:3]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[CH:4]=[CH:5][N:6]=1

Participants

6

Reactant 4

HCID 127492-MethylimidazoleHCID 24758Sodium hydrideHCID 677943-FluoropyridineHCID 516892Sodium Bicarbonate

Product 1

HCID 166546863-(2-Methyl-1H-imidazol-1-yl)pyridineYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 2-methylimidazole (256 mg, 3.13 mmol) in DMF (5 mL) was added NaH (60% dispersion in mineral oil, 180 mg, 4.50 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 (88 μL, 1.01 mmol) in DMF (1 mL), the resultant solution was heated to 100° C. and stirred overnight. The solution was cooled to rt, 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/CHCl3, 5/95, Rf=0.12) to afford the title compound 62 (48 mg, 30% yield) as a yellow oil: 1H NMR (CDCl3) δ 8.69 (m, 1H), 8.63 (m, 1H), 7.64 (m, 1H), 7.45 (m, 1H), 7.07 (m, 1H), 7.02 (m, 1H), 2.38 (s, 3H); LRMS (ESI) m/z calcd for C9H10N3 [M+H]+ 160. found 160; HRMS (ESI) m/z calcd for C9H10N3 [M+H]+ 160.0875. found 160.0866; HPLC>99% (tR=7.75 min, 55 (A):45 (B): 0.032 (C); tR=5.45 min, 55 (A):45 (B): 0.01 (C)).

Workup

  1. extractionextracted with ethyl acetate (3×50 mL)
  2. washwashed with brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent was removed in vacuo
  6. customThe crude material was chromatographed on silica gel (CH3OH/CHCl3, 5/95, Rf=0.12)

Sources & evidence

ORD record
ord-1ef602516c184ba3b3b8ec63168857a8
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

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