Imidazole → HCID 59472788, compound

HRID 885144Notes

Reaction equation

HRID 885144 reaction equation
Cl[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][N:3]=1.[CH3:10][C:11]1[N:12]=[CH:13][NH:14][CH:15]=1.[C:16]([O-])([O-])=O.[K+].[K+].N1C=CN=C1.[N+](=C(P(=O)(OC)OC)C(=O)C)=[N-]>CN(C=O)C.CCOC(C)=O.CO.C(Cl)Cl>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([N:14]2[CH:15]=[C:11]([CH3:10])[N:12]=[CH:13]2)=[N:3][CH:4]=1)#[CH:16]

Participants

10

Reactant 5

HCID 795ImidazoleHCID 11430Potassium Carbonate2×HCID 27640536-Chloropyridine-3-carbaldehydeHCID 136023029(1E)-1-diazo-1-dimethoxyphosphorylpropan-2-oneHCID 178418800HCID 178418800, compound

Product 1

HCID 59472788HCID 59472788, compoundYield 56%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 6-chloronicotinaldehyde (5.0 g, 35 mmol) in 60 mL of DMF was treated with 4-methylimidazole (5.8 g, 71 mmol) and K2CO3 (7.3 g, 53 mmol) and warmed to 100° C. Stirred overnight. Diluted with EtOAc, washed with sat'd NaHCO3, dried (Na2SO4), concentrated to give a 4:1 mixture of imidazole regioisomers. Recrystallization from EtOH gave a single regioisomer. A portion of the aldehyde (500 mg, 2.67 mmol) was dissolved in 10 mL of MeOH, treated with K2CO3 (740 mg, 5.4 mmol) and dimethyl (1-diazo-2-oxopropyl)phosphonate (620 mg, 3.2 mmol) and stirred overnight. Diluted with DCM and washed with water. Dried (Na2SO4), conc. Chromatography on silica (0-20% MeOH/DCM) gave the desired alkyne (276 mg; 56%):

Workup

  1. washwashed with sat'd NaHCO3
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customto give
  5. customRecrystallization from EtOH
  6. customgave a single regioisomer
  7. stirringstirred overnight
  8. washwashed with water
  9. dry with materialDried (Na2SO4), conc. Chromatography on silica (0-20% MeOH/DCM)

Sources & evidence

ORD record
ord-1d3c0855e33f4a63878432e60f371223
Source dataset
uspto-grants-2012_08
Patent number
US08242150B2

Reaction notes

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