1-Methylimidazole → HCID 22048491, compound

HRID 1830817Notes

Reaction equation

HRID 1830817 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.[Li]CCCC.Cl[Si](CC)(CC)CC.[Cl:20][C:21]1[CH:22]=[C:23]([C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[C:34]([C:37]([C:39]4[N:43]([CH3:44])[CH:42]=[N:41][CH:40]=4)=[O:38])[CH:35]=3)[N:30]([CH3:45])[C:29](=[O:46])[CH:28]=2)[CH:24]=[CH:25][CH:26]=1>C1COCC1>[Cl:20][C:21]1[CH:22]=[C:23]([C:27]2[C:36]3[C:31](=[CH:32][CH:33]=[C:34]([C:37]([OH:38])([C:3]4[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=4)[C:39]4[N:43]([CH3:44])[CH:42]=[N:41][CH:40]=4)[CH:35]=3)[N:30]([CH3:45])[C:29](=[O:46])[CH:28]=2)[CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 22048462HCID 22048462, compoundHCID 178418339Butyllithium2×

Product 1

HCID 22048491HCID 22048491, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

A mixture of 1-methyl-1H-imidazole (0.0054 mol) in THF (10 ml) was cooled to −70° C. BuLi 1.6M (3.4 ml) was added dropwise and the mixture stood at −70° C. for 30 min. Chlorotriethylsilane (0.0054 mol) was added. The mixture was allowed to warm to 10° C. and then cooled to −70° C. BuLi 1.6M (3.4 ml) was added dropwise. The mixture stood at −70° C. for 1 hour, brought quickly to −15° C. and cooled to −70° C. THF (20 ml) and then intermediate 29) (0.0045 mol) were added. The mixture was allowed to warm to room temperature, stirred at room temperature overnight, stirred and refluxed for 24 hours, then hydrolized and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue (2.7 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.5; 15–40 μm). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from 2-propanone/DIPE. The precipitate was filtered off and dried, yielding 0.6 g (28%) of 4-(3-chlorophenyl)-6-[hydroxy(1-methyl-1H-imidazol-2-yl)(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone, melting point 130° C.

Workup

  1. temperatureto warm to 10° C.
  2. temperaturecooled to −70° C
  3. waitThe mixture stood at −70° C. for 1 hour
  4. custombrought quickly to −15° C.
  5. temperaturecooled to −70° C
  6. temperatureto warm to room temperature
  7. stirringstirred
  8. temperaturerefluxed for 24 hours
  9. extractionhydrolized and extracted with DCM
  10. customThe organic layer was separated
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customthe solvent was evaporated till dryness
  14. customThe residue (2.7 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.5; 15–40 μm)
  15. customThe pure fractions were collected
  16. customthe solvent was evaporated
  17. customThe residue was crystallized from 2-propanone/DIPE
  18. filtrationThe precipitate was filtered off
  19. customdried

Sources & evidence

ORD record
ord-60f21c8edc964efc99d9a6f2ba37ebab
Source dataset
uspto-grants-2006_06
Patent number
US07067531B2

Reaction notes

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