5-Bromo-1-methyl-1H-imidazole → (1-Methyl-1H-imidazol-5-yl)(tetrahydro-2H-pyran-4-yl)methanone

HRID 926443Notes

Reaction equation

HRID 926443 reaction equation
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C([Mg]Br)C.CON(C)[C:15]([CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1)=[O:16]>C1COCC1>[CH3:7][N:6]1[C:2]([C:15]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])=[CH:3][N:4]=[CH:5]1

Participants

5

Reactant 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 23144693N-methoxy-N-methyloxane-4-carboxamideHCID 178418443HCID 178418443, compound

Product 1

HCID 82895191(1-Methyl-1H-imidazol-5-yl)(tetrahydro-2H-pyran-4-yl)methanone

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A clear colorless solution of 5-bromo-1-methyl-1H-imidazole (1.12 g, 6.93 mmol) in THF (10 mL) was placed in an ice bath and ethylmagnesium bromide (3.0 M in Et2O, 2.31 mL, 6.93 mmol) was added via syringe. The reaction mixture was stirred for 20 minutes at room temperature. N-Methoxy-N-methyltetrahydro-2H-pyran-4-carboxamide (1.0 g, 5.8 mmol, Intermediate 1: step a, Procedure A) was added neat by syringe (using 1 mL THF rinse to quantitate transfer), and the resulting white suspension was stirred at room temperature for 2 days. The mixture was diluted with saturated aqueous NH4Cl followed by water, then was extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated to dryness. The crude product was purified by flash column chromatography two times (1-4% MeOH-DCM first column; 40-60% CH3CN-DCM second column) to provide the title compound as a white crystalline solid.

Workup

  1. wash(using 1 mL THF rinse to quantitate transfer)
  2. stirringthe resulting white suspension was stirred at room temperature for 2 days
  3. additionThe mixture was diluted with saturated aqueous NH4Cl
  4. extractionwas extracted with EtOAc (3×)
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by flash column chromatography two times (1-4% MeOH-DCM first column; 40-60% CH3CN-DCM second column)

Sources & evidence

ORD record
ord-5956a8c13c0b42f6ab5c1242bb085cb7
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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