Benzimidazole → ethyl 2-[4-(1H-benzimidazol-1-ylmethyl)phenyl]-1,3-oxazole-4-carboxylate

HRID 1716826Notes

Reaction equation

HRID 1716826 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.[H-].[Na+].Cl[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[O:21][CH:22]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:24]=2)=[CH:16][CH:15]=1>CN(C=O)C>[N:1]1([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[O:21][CH:22]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:24]=3)=[CH:18][CH:19]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 46834790Ethyl 2-[4-(chloromethyl)phenyl]-1,3-oxazole-4-carboxylate

Product 1

HCID 44595568ethyl 2-[4-(1H-benzimidazol-1-ylmethyl)phenyl]-1,3-oxazole-4-carboxylateYield 92.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of benzimidazole (1.5 eq) in DMF was added portionwise sodium hydride (60% suspension in mineral oil, 1.5 eq) and the reaction mixture was allowed to stir for 45 min at room temperature. The reaction mixture was then added to a solution of ethyl 2-[4-(chloromethyl)phenyl]-1,3-oxazole-4-carboxylate (1 eq) in DMF and the reaction mixture was allowed to stir at room temperature for 2 h. The reaction mixture was poured into ice/water, stirred for 30 min, and the resulting precipitate filtered through a coarse filter without vacuum suction (if the filtration is bad, it is possible to decant the aqueous/DMF layer from the organic precipitate), the precipitate dissolved in methylene chloride, washed with aq. ammonium chloride, water, dried over sodium sulphate, evaporated, triturated with MTBE, filtered, dried in the oven at 40° C. overnight. The product (92.4% yield) was obtained as off-white crystals; m.p. 150-152° C. 1H NMR (300 MHz, DMSO-D6, δ): 8.92 (s, 1H), 8.45 (d, 2H, J=8.5 Hz), 7.99 (d, 2H, J=8.5 Hz), 7.68 (m, 1H), 7.51 (m, 1H), 7.46 (d, 2H, J=8.5 Hz), 7.21 (m, 2H), 5.61 (s, 2H), 4.31 (m, 2H, J=7.2 Hz), 3.32 (s, 2H), 130 (t, 3H, J=7.2 Hz).

Workup

  1. stirringto stir at room temperature for 2 h
  2. stirringstirred for 30 min
  3. filtrationthe resulting precipitate filtered through
  4. filtrationa coarse filter without vacuum suction (
  5. filtrationif the filtration
  6. customto decant the aqueous/DMF layer from the organic precipitate), the precipitate
  7. dissolutiondissolved in methylene chloride
  8. washwashed with aq. ammonium chloride, water
  9. dry with materialdried over sodium sulphate
  10. customevaporated
  11. customtriturated with MTBE
  12. filtrationfiltered
  13. customdried in the oven at 40° C. overnight

Sources & evidence

ORD record
ord-eca0f842abbe413da7fcf5e814d45c09
Source dataset
uspto-grants-2010_09
Patent number
US07803825B2

Reaction notes

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