1-Methylimidazole → (+/-)-alpha-(4-chlorophenyl)-1-methyl-alpha-(4-nitrophenyl)-1H-imidazole-5-methanol

HRID 429850

Reaction equation

HRID 429850 reaction equation
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[CH:3]1.Cl[Si](CC)(CC)CC.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]([C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)=[O:23])=[CH:18][CH:17]=1>CCCCCC.C1COCC1>[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)([C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[OH:23])=[CH:20][CH:21]=1.[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([C:22]([C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)([C:6]2[N:2]([CH3:1])[CH:3]=[N:4][CH:5]=2)[OH:23])=[CH:20][CH:21]=1

Participants

7

Reactant 3

HCID 13901-MethylimidazoleHCID 13819ChlorotriethylsilaneHCID 3477714-Chloro-4'-nitrobenzophenone

Product 2

HCID 22335519(+/-)-alpha-(4-chlorophenyl)-1-methyl-alpha-(4-nitrophenyl)-1H-imidazole-5-methanolYield 26.6%HCID 22335528(+/-)-alpha-(4-chlorophenyl)-1-methyl-alpha-(4-nitrophenyl)-1H-imidazole-2-methanolYield 20%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent2×

Conditions

Temperature
-70 °C

Procedure

n-Buthyl-lithium in hexane (1.6M; 71.6 ml) was added dropwise at −70° C. under N2 flow to a mixture of 1-methylimidazole (0.1146 mol) in THF (195 ml). The mixture was stirred at −70° C. for 30 minutes. Chlorotrietylsilane (0.1146 mol) was added. The mixture was brought slowly to 10° C. and cooled again to −70° C. n-Buthyl-lithium in hexane (1.6M; 71.6 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 mixture of 4-chlorophenyl-4-nitrophenyl-methanone (0.095 mol) in THF (150 ml) was added dropwise. The mixture was stirred at −70° C. for 30 minutes, hydrolized and extracted with EtOAc. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH NH4OH 96/4/0.1). The desired fractions were collected and their solvents were evaporated, yielding 6.5 g (20%) of (±)-α-(4-chlorophenyl)-1-methyl-α-(4-nitrophenyl)-1H-imidazole-2-methanol (interm 12), 8.7 g (26.6%) of (±)-α-(4-chlorophenyl)-1-methyl-α-(4-nitrophenyl)-1H-imidazole-5-methanol (interm 13) and 18 g (53%) of the mixture of intermediate 12 and 13.

Workup

  1. customwas brought slowly to 10° C.
  2. additionwas added dropwise
  3. stirringThe mixture was stirred at −70° C. for 1 hour
  4. custombrought to −15° C.
  5. temperaturecooled again to −70° C
  6. additionwas added dropwise
  7. stirringThe mixture was stirred at −70° C. for 30 minutes
  8. extractionhydrolized and extracted with EtOAc
  9. customThe organic layer was separated
  10. customdried
  11. filtrationfiltered
  12. customthe solvent was evaporated
  13. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH NH4OH 96/4/0.1)
  14. customThe desired fractions were collected
  15. customtheir solvents were evaporated

Sources & evidence

ORD record
ord-62f451276cd142289abc9377b3d507ce
Source dataset
uspto-grants-2001_11
Patent number
US06319939B1

Linked notes

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