Hydrochloric Acid → 3-(1-ethylimidazol-4-yl)pyridine

HRID 1913371Notes

Reaction equation

HRID 1913371 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+].I[CH2:15][CH3:16].Cl>C1COCC1.O>[CH2:15]([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)[CH3:16]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 24758Sodium hydrideHCID 178420772HCID 178420772, compound

Product 1

HCID 114807323-(1-ethylimidazol-4-yl)pyridineYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 34 (36 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. Iodoethane (26 μL, 0.32 mmol) was added and the resultant solution was stirred for 10 min. The reaction was stopped by the careful addition of aqueous hydrochloric acid (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 was adjusted to pH 9 with NaOH(aq) (10 N). The organic fraction was collected and the aqueous fraction 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=0.27) to afford the title compound 59 (34 mg, 79% yield) as a clear oil: 1H NMR (CDCl3) δ 8.93 (m, 1H), 8.44 (m, 1H), 8.07 (m, 1H), 7.54 (br s, 1H), 7.28 (m, 2H), 4.02 (q, J=7.4 Hz, 2H), 1.49 (t, J=7.4 Hz, 3H); LRMS (ESI) m/z calcd for C10H11N3 [M+H]+ 174. found 174; HRMS (ESI) m/z calcd for C10H11N3 [M+H]+ 174.1031. found 174.1042; HPLC>97% (tR=13.28 min, 60 (A):40 (B): 0.02 (C); tR=3.67 min, 80 (A):20 (B): 0.1 (C).

Workup

  1. washwashed with ethyl acetate (3×15 ml)
  2. additionDichloromethane was added (25 mL)
  3. customThe organic fraction was collected
  4. extractionthe aqueous fraction was extracted with dichloromethane (20 mL)
  5. dry with materialthe combined organic fractions were dried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent was removed in vacuo
  8. customThe crude material was chromatographed on silica gel (CH3OH/CHCl3, 2.5/97.5, Rf=0.27)

Sources & evidence

ORD record
ord-24415f884a024d7b86ce257658a165bb
Source dataset
uspto-grants-2013_12
Patent number
US08609708B2

Reaction notes

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