4-Methylmorpholine → 4-(4-Bromophenyl)-N-methoxy-N,1-dimethyl-1H-imidazole-2-carboxamide

HRID 222896Notes

Reaction equation

HRID 222896 reaction equation
[Na].[Br:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]([C:15]([OH:17])=O)[N:12]([CH3:14])[CH:13]=2)=[CH:5][CH:4]=1.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[CH3:34][NH:35][O:36][CH3:37]>C(Cl)Cl>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:10]=[C:11]([C:15]([N:35]([CH3:34])[O:36][CH3:37])=[O:17])[N:12]([CH3:14])[CH:13]=2)=[CH:7][CH:8]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 5360545SodiumHCID 67277590HCID 67277590, compound

Product 1

HCID 575944134-(4-Bromophenyl)-N-methoxy-N,1-dimethyl-1H-imidazole-2-carboxamideYield 32%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of ethyl 4-(4-bromophenyl)-1-methyl-1H-imidazole-2-carboxylate (1.66 g, 5.37 mmol) in MeOH (38 mL) was added 1N NaOH solution (19 mL). The reaction turned cloudy white and was stirred at room temperature for 30 minutes. The reaction mixture was concentrated in vacuo and pumped under high vacuum overnight to give the sodium salt of 4-(4-bromophenyl)-1-methyl-1H-imidazole-2-carboxylic acid as a white solid. The sodium salt of 4-(4-bromophenyl)-1-methyl-1H-imidazole-2-carboxylic acid was dissolved in anhydrous CH2Cl2 (40 mL) under nitrogen at −15° C. (ice/methanol bath) and N-methylmorpholine (1.1 equiv, 5.91 mmol) was added followed by isobutyl chloroformate (1.1 equiv, 5.91 mmol). The reaction mixture was stirred at −15° C. for 15 minutes and then N,O-dimethylhydroxylamine hydrochloride (1.0 equiv, 5.37 mmol) was added. The reaction was allowed to warm to room temperature and was stirred for 17 hours. The reaction was quenched with H2O (10 mL). The product was extracted using EtOAc (3×30 mL) and the combined organic layers were washed with brine (20 mL), dried over MgSO4, and concentrated in vacuo. Purification by silica gel chromatography (Analogix IF280, 20-100% EtOAc/hexanes) afforded the title compound as a tan solid (32%). ESMS [M+H]+: 324.2.

Workup

  1. additionwas added
  2. temperatureto warm to room temperature
  3. stirringwas stirred for 17 hours
  4. customThe reaction was quenched with H2O (10 mL)
  5. extractionThe product was extracted
  6. washthe combined organic layers were washed with brine (20 mL)
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography (Analogix IF280, 20-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-78db3eabca72445ab87ee06cb57fae14
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Reaction notes

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