Water → 2-[4-(2,6-Dichlorobenzyl)piperazin-1-yl]-6-trifluoromethyl-1H-benzoimidazole

HRID 730704Notes

Reaction equation

HRID 730704 reaction equation
[N:1]1([C:7]2[NH:11][C:10]3[CH:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:9]=3[N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:20][C:21]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:22]=1[CH2:23]Br.C([O-])(O)=O.[Na+].O>CN(C=O)C>[Cl:20][C:21]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:22]=1[CH2:23][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[NH:11][C:10]3[CH:12]=[C:13]([C:16]([F:19])([F:17])[F:18])[CH:14]=[CH:15][C:9]=3[N:8]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 962WaterHCID 301591-Bromomethyl-2,6-dichlorobenzeneHCID 516892Sodium BicarbonateHCID 116662012-Piperazin-1-yl-6-trifluoromethyl-1H-benzoimidazole

Product 1

HCID 578351142-[4-(2,6-Dichlorobenzyl)piperazin-1-yl]-6-trifluoromethyl-1H-benzoimidazole

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the benzoimidazole from step (a) above (96 mg, 0.36 mmol), 2,6-dichlorobenzyl bromide (86 mg, 0.36 mmol, Aldrich) and NaHCO3 (151 mg, 1.8 mmol) in DMF (2 mL) was stirred at room temperature for 16 h. Water (10 mL) was then added and the mixture was extracted with EtOAc (2×20 mL). The combined organic phases were washed with water (5 mL) and brine (5 mL) then dried over Na2SO4 and filtered. The solvent was removed in vacuo and the residue purified by silica gel chromatography, eluting with 40% EtOAc/hexane. The material was recrystallized from EtOAc/hexanes to give the title compound as a white solid. M.p. 254-256° C. MS (ESI, pos. ion) m/z: 429 (M+1).

Workup

  1. extractionthe mixture was extracted with EtOAc (2×20 mL)
  2. washThe combined organic phases were washed with water (5 mL) and brine (5 mL)
  3. dry with materialthen dried over Na2SO4
  4. filtrationfiltered
  5. customThe solvent was removed in vacuo
  6. customthe residue purified by silica gel chromatography
  7. washeluting with 40% EtOAc/hexane
  8. customThe material was recrystallized from EtOAc/hexanes

Sources & evidence

ORD record
ord-af1eb4f0e7624a048bf98ab324ed4cea
Source dataset
uspto-grants-2009_09
Patent number
US07582761B2

Reaction notes

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