Hydrochloric Acid → 1-(4-Trifluoromethoxybenzyl)-1,3-dihydrobenzimidazol-2-one

HRID 221965Notes

Reaction equation

HRID 221965 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]1=[O:10].[F:11][C:12]([F:23])([F:22])[O:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18]Br)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].Cl>O.CN(C=O)C>[F:11][C:12]([F:22])([F:23])[O:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[NH:3][C:2]2=[O:10])=[CH:16][CH:15]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 119852-Hydroxy benzimidazoleHCID 1427851-(Bromomethyl)-4-(trifluoromethoxy)benzene

Product 1

HCID 597070591-(4-Trifluoromethoxybenzyl)-1,3-dihydrobenzimidazol-2-oneYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of benzimidazolinone (4.02 g, 30 mmol) in abs. DMF (20 mL) there were added 4-trifluoromethoxybenzyl bromide (5 g, 19.6 mmol), potassium carbonate (7.0 g, 50.7 mmol), and a catalytic amount of potassium iodide under a blanket of argon. The reaction mixture was heated to 100° C. over a period of 2 h. Following cooling, the reaction mixture was poured into a mixture of ice (200 g) and 2N hydrochloric acid solution in H2O (100 mL). The resulting precipitate was separated with the aid of a frit and then dried. The residue was taken up in EtOAc (150 mL) and the insoluble components separated. The solvent was removed in vacuo, and the residue was recrystallized from a little EtOAc (20 mL), and the dibenzylated product (S) was precipitated. The mother liquor was again concentrated in vacuo, the residue recrystallized from ethanol, and the precipitated solid matter (S) separated by filtration. The filtrate was purified by means of column chromatography (SiO2, cyclohexane/EtOAc 1:4), and there was obtained 1-(4-trifluoromethoxybenzyl)-1,3-dihydrobenzimidazol-2-one (R) (1.60 mg, 26% of theory, mp: 145-148° C.).

Workup

  1. temperatureFollowing cooling
  2. customThe resulting precipitate was separated with the aid of a frit
  3. customdried
  4. customthe insoluble components separated
  5. customThe solvent was removed in vacuo
  6. customthe residue was recrystallized from a little EtOAc (20 mL)
  7. customthe dibenzylated product (S) was precipitated
  8. concentrationThe mother liquor was again concentrated in vacuo
  9. customthe residue recrystallized from ethanol
  10. customthe precipitated solid matter (S) separated by filtration
  11. customThe filtrate was purified by means of column chromatography (SiO2, cyclohexane/EtOAc 1:4)

Sources & evidence

ORD record
ord-22545cd2fae24bc29a6e0e9a23bdd3de
Source dataset
uspto-grants-2012_06
Patent number
US08207182B2

Reaction notes

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