Benzyl Bromide → 3-(1-benzyl-1H-imidazol-4-yl)pyridine

HRID 1913372Notes

Reaction equation

HRID 1913372 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[N:3]=[CH:2]1.[H-].[Na+].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>C1COCC1>[CH2:14]([N:1]1[CH:5]=[C:4]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)[N:3]=[CH:2]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 178420772HCID 178420772, compound

Product 1

HCID 112070723-(1-benzyl-1H-imidazol-4-yl)pyridineYield 74%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 34 (35 mg, 0.25 mmol) in THF (5 mL) under argon was added sodium hydride (12 mg, 0.29 mmol) in one portion and the resultant slurry was stirred for 20 min. Benzyl bromide (26 μL, 0.32 mmol) was added and the resultant solution was stirred for 10 min. The reaction was quenched by the slow addition of HCl(aq) (1 N, 2 mL), diluted with 13 mL of water and washed with ethyl acetate (3×15 ml). Dichloromethane was added (25 mL) and the aqueous fraction was adjusted to pH 9 with NaOH(aq) (10 N). The organic fraction was collected and the aqueous was extracted with dichloromethane (20 mL), the combined organic fractions were dried (Na2SO4), filtered and the solvent was removed in vacuo. The crude material was chromatographed on silica gel (CH3OH/CHCl3, 2.5/97.5, Rf=0.26) to afford the title compound 60 (43 mg, 74% yield) as a white semisolid: 1H NMR (CDCl3) δ 8.95 (br s, 1H), 8.47 (br s, 1H), 8.10 (m, 1H) 7.64 (m, 1H) 7.42-7.17 (m, 7H) 5.17 (s, 2H); LRMS (ESI) m/z calcd for C15H14N3 [M+H]+ 236. found 236; HRMS (ESI) m/z calcd for C15H14N3 [M+H]+ 236.1188. found 236.1198; HPLC>99% (tR=10 min, 60 (A):40 (B): 0.02 (C); tR=6.12 min, 60 (A):40 (B): 0.07 (C)).

Workup

  1. customThe reaction was quenched by the slow addition of HCl(aq) (1 N, 2 mL)
  2. additiondiluted with 13 mL of water
  3. washwashed with ethyl acetate (3×15 ml)
  4. additionDichloromethane was added (25 mL)
  5. customThe organic fraction was collected
  6. extractionthe aqueous was extracted with dichloromethane (20 mL)
  7. dry with materialthe combined organic fractions were dried (Na2SO4)
  8. filtrationfiltered
  9. customthe solvent was removed in vacuo
  10. customThe crude material was chromatographed on silica gel (CH3OH/CHCl3, 2.5/97.5, Rf=0.26)

Sources & evidence

ORD record
ord-d5cda954f19948889717d3aff1d7563b
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

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