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2-Butyl-4-chloro-5-(hydroxymethyl)imidazole → 2-Butyl-1-[4-(2-carbomethoxybenzoyl)benzyl]-4-chloro-5-hydroxymethylimidazole

HRID 653918
Notes
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Reaction equation

HRID 653918 reaction equation
[CH2:1]([C:5]1[NH:6][C:7]([CH2:11][OH:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4].C[O-].[Na+].Br[CH2:17][C:18]1[CH:35]=[CH:34][C:21]([C:22]([C:24]2[CH:33]=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([O:28][CH3:29])=[O:27])=[O:23])=[CH:20][CH:19]=1>CO.CN(C=O)C>[CH2:1]([C:5]1[N:6]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:22](=[O:23])[C:24]3[CH:33]=[CH:32][CH:31]=[CH:30][C:25]=3[C:26]([O:28][CH3:29])=[O:27])=[CH:34][CH:35]=2)[C:7]([CH2:11][OH:12])=[C:8]([Cl:10])[N:9]=1)[CH2:2][CH2:3][CH3:4]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 27356622-Butyl-4-chloro-5-(hydroxymethyl)imidazoleHCID 10942334Sodium MethoxideHCID 19012308Methyl 2-(4-(bromomethyl)benzoyl)benzoate

Product 1

HCID 198152912-Butyl-1-[4-(2-carbomethoxybenzoyl)benzyl]-4-chloro-5-hydroxymethylimidazoleYield 61.8%

Reagents, catalysts & solvents 2

HCID 887Methanol
Solvent
HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-butyl-4-chloro-5-(hydroxymethyl)imidazole (11.12 g, 54 mmol, 1 eq) in 200 mL methanol was added dropwise a freshly prepared sodium methoxide solution (1.36 g Na, 59mmol, 1.1 eq in 50 mL MeOH). After stirring for 0.5 hours, the methanol was removed in vacuo and the resultant glass was dissolved in 200 mL DMF. To this mixture was added a solution of methyl 2-[4-(bromomethyl)benzoyl]benzoate (18.00 g, 59 mmol, 1.1 eq) in DMF and the entire contents was stirred overnight under N2 at room temperature. The solvent was then removed in vacuo and the residue dissolved in 500 mL ethyl acetate and 500 mL H2O. The layers were separated and the aqueous layer was extracted twice with 500 mL portions of ethyl acetate. The organic layers were dried and concentrated and the crude product flash chromatographed to separate the two regioisomers in 60:40 hexane/ethyl acetate over silica gel. The faster moving isomer was isolated to yield 14.72 g of a glassy solid. NWR (200 MHz, CDCl3) δ8.03 (d, 1H, J=7Hz); 7.67 (m, 4H); 7.36 (d, 1H, J=7Hz); 7.05 (d, 2H, J=7Hz); 5.28 (s, 2H); 4.43 (s, 2H); 3.63 (s, 3H); 2.53 (t, 2H, J=7Hz,); 1.60 (t of t, 2H, J=7,7Hz); 1.30 (t of q, 2H, J=7,7Hz); 0.87 (t, 3H, J=7Hz). Mass Calcd. for C25H26ClF3N4O5S: 586.1264. Found: 586.1285.

Workup

  1. customthe methanol was removed in vacuo
  2. dissolutionthe resultant glass was dissolved in 200 mL DMF
  3. stirringthe entire contents was stirred overnight under N2 at room temperature
  4. customThe solvent was then removed in vacuo
  5. dissolutionthe residue dissolved in 500 mL ethyl acetate
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted twice with 500 mL portions of ethyl acetate
  8. customThe organic layers were dried
  9. concentrationconcentrated
  10. customthe crude product flash chromatographed
  11. customto separate the two regioisomers in 60:40 hexane/ethyl acetate over silica gel
  12. customwas isolated

Sources & evidence

ORD record
ord-af969166a28f464db9daf046b2958cf2
Source dataset
uspto-grants-1992_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05128355

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes