1-methyl-1H-imidazole-5-carbaldehyde → (1-Methyl-1H-imidazol-5-yl)(2-(trifluoromethyl)pyridin-4-yl)methanol

HRID 928808Notes

Reaction equation

HRID 928808 reaction equation
C([Mg]Cl)(C)C.[Cl-].[Li+].Br[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=1.[CH3:19][N:20]1[C:24]([CH:25]=[O:26])=[CH:23][N:22]=[CH:21]1>C1COCC1>[CH3:19][N:20]1[C:24]([CH:25]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[OH:26])=[CH:23][N:22]=[CH:21]1

Participants

5

Reactant 3

HCID 5735921-methyl-1H-imidazole-5-carbaldehydeHCID 234369504-Bromo-2-(trifluoromethyl)pyridineHCID 178461733HCID 178461733, compound

Product 1

HCID 86715639(1-Methyl-1H-imidazol-5-yl)(2-(trifluoromethyl)pyridin-4-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of isopropylmagnesium chloride/lithium chloride complex (1.3 M in THF, 10.6 mL, 13.8 mmol) was added dropwise by syringe to a solution of 4-bromo-2-(trifluoromethyl)pyridine (3.12 g, 13.8 mmol) in dry THF (50 mL) at 0° C. After 30 min, a solution of 1-methyl-1H-imidazole-5-carbaldehyde in THF (1.38 g, 12.5 mmol) was added to the Grignard solution by syringe at 0° C. The reaction mixture was warmed to room temperature over 2 h after which it was quenched with saturated aqueous ammonium chloride solution. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate and washed with saturated aqueous NaCl solution. The organic phase was dried (MgSO4), filtered, and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-10% MeOH-DCM) to provide the title compound.

Workup

  1. customwas quenched with saturated aqueous ammonium chloride solution
  2. customThe mixture was partitioned between water and ethyl acetate
  3. extractionThe separated aqueous phase was further extracted with ethyl acetate
  4. washwashed with saturated aqueous NaCl solution
  5. dry with materialThe organic phase was dried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography (silica gel, 0-10% MeOH-DCM)

Sources & evidence

ORD record
ord-3c7e6a5fdf54405fb8856826304f169f
Source dataset
uspto-grants-2016_03
Patent number
US09290476B2

Reaction notes

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