5-Bromo-1-methyl-1H-imidazole → HCID 86716092, compound

HRID 627526Notes

Reaction equation

HRID 627526 reaction equation
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C([Mg]Cl)(C)C.[Li+].[Cl-].[Cl:15][C:16]1[C:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:24]([Cl:32])[C:23]2[C:18](=[C:19]([CH3:35])[CH:20]=[C:21]([CH:33]=[O:34])[CH:22]=2)[N:17]=1>C(Cl)Cl>[Cl:15][C:16]1[C:25]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:24]([Cl:32])[C:23]2[C:18](=[C:19]([CH3:35])[CH:20]=[C:21]([CH:33]([C:2]3[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=3)[OH:34])[CH:22]=2)[N:17]=1

Participants

5

Reactant 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 86716090HCID 86716090, compound2×HCID 178461733HCID 178461733, compound

Product 1

HCID 86716092HCID 86716092, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-bromo-1-methyl-1H-imidazole (342 mg, 2.12 mmol) in DCM (2.2 mL) was stirred on an ice bath while iPrMgCl—LiCl (1.77 mL, 1.2 M in THF, 2.1 mmol) was added dropwise over 1-2 min under argon. After 10 min stirring at room temperature, the homogeneous amber reaction was added dropwise over 1-2 min to a slurry of 2,4-dichloro-8-methyl-3-phenylquinoline-6-carbaldehyde (460 mg, 1.46 mmol, Intermediate 47, step b) in LaCl3-2LiCl (7.60 mL, 0.56 M in THF, 1.46 mmol) on an ice bath. The reaction was removed from the ice bath immediately following Grignard addition and stirred for 45 min at ambient temperature, and was then partitioned with 9:1 DCM/MeOH (14 mL) and 5 M NH4Cl (0.72 mL). This was filtered over Celite®, and the filter cake washed with 9:1 DCM/MeOH (1×5 mL). The combined clear dark yellow filtrates were dried (Na2SO4), filtered, and concentrated to provide a beige foam. This was concentrated from DCM (3×15 mL) in prelude to MnO2 oxidation.

Workup

  1. additionwas added dropwise over 1-2 min under argon
  2. customthe homogeneous amber reaction
  3. customThe reaction was removed from the ice bath immediately following Grignard addition
  4. stirringstirred for 45 min at ambient temperature
  5. customwas then partitioned with 9:1 DCM/MeOH (14 mL) and 5 M NH4Cl (0.72 mL)
  6. filtrationThis was filtered over Celite®
  7. washthe filter cake washed with 9:1 DCM/MeOH (1×5 mL)
  8. dry with materialThe combined clear dark yellow filtrates were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto provide a beige foam
  12. concentrationThis was concentrated from DCM (3×15 mL) in prelude to MnO2 oxidation

Sources & evidence

ORD record
ord-5dd054779d1443568d8d8f186a7b0e5d
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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