1-Methylimidazole → HCID 10297355, compound

HRID 1830818Notes

Reaction equation

HRID 1830818 reaction equation
[Li]CCCC.[CH3:6][N:7]1[CH:11]=[CH:10][N:9]=[CH:8]1.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[CH:43]=[CH:42][O:41][CH:40]=4)=[O:38])[CH:35]=3)[N:30]([CH3:44])[C:29](=[O:45])[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]([C:39]4[CH:43]=[CH:42][O:41][CH:40]=4)([OH:38])[C:11]4[N:7]([CH3:6])[CH:8]=[N:9][CH:10]=4)[CH:35]=3)[N:30]([CH3:44])[C:29](=[O:45])[CH:28]=2)[CH:24]=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 22048471HCID 22048471, compoundHCID 178418339Butyllithium2×

Product 1

HCID 10297355HCID 10297355, compoundYield 12.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

BuLi 1.6M (20.6 ml) was added dropwise at −70° C. under N2 flow to a mixture of 1-methyl-1H-imidazole (0.033 mol) in THF (60 ml). The mixture was stirred at −70° C. for 30 min. chlorotriethyl-silane (0.033 mol) was added. The mixture was brought slowly to 10° C. and cooled again to −70° C. BuLi 1.6M (20.6 ml) was added dropwise. The mixture was stirred at −70° C. for 1 hour, brought to −15° C. and cooled again to −70° C. A suspension of intermediate 27 (0.022 mol) in THF (80 ml) was added dropwise. The mixture was stirred at −70° C. for 30 min, then brought to room temperature, hydrolized, extracted with EtOAc and decanted. The organic layer was dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue (13 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.2; 20–45 μm). One pure fraction was collected and the solvent evaporated. The residue was crystallized from CH3CN and diethyl ether. The precipitate was filtered off and dried, yielding 1.2 g (12.2%) of 4-(3-chlorophenyl)-6-[3-furanylhydroxy(1-methyl-1H-imidazol-5-yl)methyl]-1-methyl-2(1H)-quinolinone, melting point 248° C.

Workup

  1. additionwas added
  2. customwas brought slowly to 10° C.
  3. custombrought to −15° C.
  4. temperaturecooled again to −70° C
  5. additionwas added dropwise
  6. stirringThe mixture was stirred at −70° C. for 30 min
  7. custombrought to room temperature
  8. extractionhydrolized, extracted with EtOAc
  9. customdecanted
  10. dry with materialThe organic layer was dried (MgSO4)
  11. filtrationfiltered
  12. customthe solvent was evaporated till dryness
  13. customThe residue (13 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 95/5/0.2; 20–45 μm)
  14. customOne pure fraction was collected
  15. customthe solvent evaporated
  16. customThe residue was crystallized from CH3CN and diethyl ether
  17. filtrationThe precipitate was filtered off
  18. customdried

Sources & evidence

ORD record
ord-6cfa7b3e1d414011b4b6dbf1e4811428
Source dataset
uspto-grants-2006_06
Patent number
US07067531B2

Reaction notes

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