Methanol → 2-Methyl-4-(1-methyl-1H-imidazol-2-yl)-quinolin-8-ol

HRID 1959552Notes

Reaction equation

HRID 1959552 reaction equation
C([Li])CCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.Br[C:13]1[C:22]2[C:17](=[C:18]([OH:23])[CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([CH3:24])[CH:14]=1.CO>C1COCC1.O1CCOCC1.[Cl-].[Cl-].[Zn+2]>[CH3:24][C:15]1[CH:14]=[C:13]([C:8]2[N:7]([CH3:6])[CH:11]=[CH:10][N:9]=2)[C:22]2[C:17](=[C:18]([OH:23])[CH:19]=[CH:20][CH:21]=2)[N:16]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 13901-MethylimidazoleHCID 670771594-Bromo-2-methyl-quinolin-8-olHCID 178418339Butyllithium

Product 1

HCID 1359503062-Methyl-4-(1-methyl-1H-imidazol-2-yl)-quinolin-8-ol

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
-40 °C

Procedure

n-Butyllithium (1.6 M in hexane, 6.0 mL, 9.7 mmol) was added dropwise to a stirred solution of 1-methyl-1H-imidazole (0.83 mL, 11 mmol) in anhydrous THF (60 mL) at −78° C. The reaction mixture was allowed to warm to −40° C. A solution of ZnCl2 (3.9 g, 28 mmol) in anhydrous THF (28 mL) was than added dropwise at −40° C. The reaction mixture was allowed to reach room temperature and was then transferred to a suspension of Pd(PPh4)4 (340 mg, 0.29 mmol) and 4-bromo-2-methyl-quinolin-8-ol (1.0 g, 4.2 mmol) in anhydrous dioxane (20 mL). After stirring for 90 min at 80° C., the reaction mixture was cooled to room temperature, MeOH (5 mL) was added and the solvent was removed in vacuo. The residue was partitioned between DCM (150 mL) and water (50 mL). The pH of the aqueous layer was adjusted to 11 by addition of concentrated aqueous NH3 solution and the aqueous layer was extracted with DCM (2×100 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (elution with DCM/MeOH 20:1) to give the title compound. MS (m/z): 240.2 [M+H+].

Workup

  1. additionthan added dropwise at −40° C
  2. customto reach room temperature
  3. temperaturethe reaction mixture was cooled to room temperature
  4. customthe solvent was removed in vacuo
  5. customThe residue was partitioned between DCM (150 mL) and water (50 mL)
  6. additionThe pH of the aqueous layer was adjusted to 11 by addition of concentrated aqueous NH3 solution
  7. extractionthe aqueous layer was extracted with DCM (2×100 mL)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel (elution with DCM/MeOH 20:1)

Sources & evidence

ORD record
ord-de2eb213d6f34cfa8ae57cb4c21b32da
Source dataset
uspto-grants-2013_04
Patent number
US08410134B2

Reaction notes

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