Ammonium Chloride → 1-(1-phenyl-1H-imidazo[4,5-c]pyridin-2-yl)ethanol

HRID 243041Notes

Reaction equation

HRID 243041 reaction equation
[CH3:1][Mg]Br.[C:4]1([N:10]2[C:18]3[CH:17]=[CH:16][N:15]=[CH:14][C:13]=3[N:12]=[C:11]2[CH:19]=[O:20])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl-].[NH4+]>C1COCC1>[C:4]1([N:10]2[C:18]3[CH:17]=[CH:16][N:15]=[CH:14][C:13]=3[N:12]=[C:11]2[CH:19]([OH:20])[CH3:1])[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 25517Ammonium Chloride2×HCID 122393351-Phenyl-1H-imidazo[4,5-c]pyridine-2-carbaldehydeHCID 178418573HCID 178418573, compound3×

Product 1

HCID 681576641-(1-phenyl-1H-imidazo[4,5-c]pyridin-2-yl)ethanolYield 47.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Methylmagnesium bromide (3.0M in diethyl ether, 2.1 mL, 6.36 mmol) was added to a stirred solution of 1-phenyl-1H-imidazo[4,5-c]pyridine-2-carbaldehyde (0.71 g, 3.18 mmol) in THF (25 mL) at −78° C. under nitrogen. The resulting mixture was stirred at −78° C. for 2 h then at −10° C. for 20 minutes, then re-cooled to −78° C. and additional methyl magnesium bromide (3.0M in diethyl ether, 1 mL, 3.00 mmol) added. The resultant mixture was stirred at −10° C. for 30 minutes then poured into saturated aqueous ammonium chloride solution (25 mL) and extracted with EtOAc (3×50 mL). The combined EtOAc extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was dissolved in THF (25 mL) and cooled to −78° C. and methyl magnesium bromide (3.0M in diethyl ether, 2.1 mL, 6.36 mmol) added, then stirred at −78° C. for 30 minutes followed by −10° C. for 1 h. The mixture was then poured into saturated aqueous ammonium chloride solution (25 mL) and extracted with EtOAc (3×50 mL). The combined EtOAc extracts were dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM) to give the title compound as a yellow oil (0.36 g, 47%). LCMS (method H): Rt 1.42 min, [M+H]+ 240.

Workup

  1. waitat −10° C. for 20 minutes
  2. temperaturere-cooled to −78° C.
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe resulting residue was dissolved in THF (25 mL)
  7. temperaturecooled to −78° C.
  8. stirringstirred at −78° C. for 30 minutes
  9. waitfollowed by −10° C. for 1 h
  10. extractionextracted with EtOAc (3×50 mL)
  11. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
  12. concentrationconcentrated in vacuo
  13. customThe resulting residue was purified by chromatography (SiO2 0-10% (2M ammonia in methanol) in DCM)

Sources & evidence

ORD record
ord-b66e66a26c8241528e7c29077e31d808
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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