Morpholine → ethyl 2-morpholinomethyl-1H-benzimidazole-4-carboxylate

HRID 1533781Notes

Reaction equation

HRID 1533781 reaction equation
Cl[CH2:2][C:3]1[NH:7][C:6]2[CH:8]=[CH:9][CH:10]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:5]=2[N:4]=1.[NH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1>ClC(Cl)C>[O:20]1[CH2:21][CH2:22][N:17]([CH2:2][C:3]2[NH:7][C:6]3[CH:8]=[CH:9][CH:10]=[C:11]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:5]=3[N:4]=2)[CH2:18][CH2:19]1

Participants

4

Reactant 2

HCID 8083Morpholine2×HCID 18355183Ethyl 2-(chloromethyl)-1H-benzo[D]imidazole-7-carboxylate

Product 1

HCID 18354876ethyl 2-morpholinomethyl-1H-benzimidazole-4-carboxylateYield 72.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of ethyl 2-chloromethyl-1H-benzimidazole-4-carboxylate (250 mg) in dichloroethane (2.5 ml) was added morpholine (183 mg) under ice bath cooling and the reaction mixture was stirred at ambient temperature for 15 hours. To the reaction mixture was added morpholine (91 mg) and stirred at 80° C. for 6 hours. After the reaction mixture was concentrated in vacuo, the residue was diluted with chloroform and saturated sodium hydrogen carbonate aqueous solution. The organic layer was separated and washed with brine. The solution was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (methanol:chloroform=1:9) to give ethyl 2-morpholinomethyl-1H-benzimidazole-4-carboxylate (219 mg).

Workup

  1. temperaturecooling
  2. stirringstirred at 80° C. for 6 hours
  3. concentrationAfter the reaction mixture was concentrated in vacuo
  4. additionthe residue was diluted with chloroform and saturated sodium hydrogen carbonate aqueous solution
  5. customThe organic layer was separated
  6. washwashed with brine
  7. dry with materialThe solution was dried over magnesium sulfate
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel column chromatography (methanol:chloroform=1:9)

Sources & evidence

ORD record
ord-4a1d95e44df846f88517fd6e2524f794
Source dataset
uspto-grants-2001_03
Patent number
US06207693B1

Reaction notes

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