3-Chloro-4-fluoroaniline → 2-(1H-benzimidazol-1-yl)-N-(3-chloro-4-fluorophenyl)acetamide

HRID 1991213Notes

Reaction equation

HRID 1991213 reaction equation
FC(F)(F)C([O-])=O.[C:8]([CH2:11][N:12]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[NH+:14]=[CH:13]1)([OH:10])=O.[Cl:21][C:22]1[CH:23]=[C:24]([CH:26]=[CH:27][C:28]=1[F:29])[NH2:25]>C(Cl)(=O)C(Cl)=O.ClCCl.C1COCC1>[N:12]1([CH2:11][C:8]([NH:25][C:24]2[CH:26]=[CH:27][C:28]([F:29])=[C:22]([Cl:21])[CH:23]=2)=[O:10])[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[N:14]=[CH:13]1

Participants

6

Reactant 2

HCID 97083-Chloro-4-fluoroanilineHCID 1785258373-carboxymethyl-3H-benzoimidazol-1-ium trifluoro-acetate

Product 1

HCID 64576052-(1H-benzimidazol-1-yl)-N-(3-chloro-4-fluorophenyl)acetamideYield 20%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 65578Oxalyl chlorideSolvent

Procedure

3-Carboxymethyl-3H-benzoimidazol-1-ium trifluoro-acetate (128 mg, 0.44 mmol) was dissolved in a mixture of oxalyl chloride (0.6 mL) and dichloromethane (3.4 mL). The reaction mixture was stirred for 30 min at ambient temperature and the solvent was evaporated. The residue was dissolved in a mixture of dichloromethane (2.5 mL) and anhydrous TBF (2.5 mL) and added to a mixture of 3-chloro4-fluoro-aniline (17 mg, 0.12 mmol) and N,N-(diisopropyl)aminomethylpolystyrene resin (140 mg, Argonaut Technologies, Inc) in anhydrous THF (3 mL). The mixture was shaken overnight. The resin was filtered off, the solvents were evaporated and the crude product was purified on a preparative LC/MS (XTerra Cs column 19×100mm, 0.1 M aqueous NH4Ac/CH3CN). The pooled fractions were lyophilized to afford 7.2 mg (20%) of the title compound. Calculated for C15H11ClFN3O m/z: 303.7, found 304.7 [M+H]+. 1H NMR (400 M, MeOD) δ ppm 5.2 (s, 2H), 7.2 (t, J=9.1 Hz, 1H), 7.3 (m, 2H), 7.5 (m, 1H), 7.5 (d, J=7.1 Hz, 1H), 7.7 (d, J=7.1 Hz, 1H), 7.8 (dd, J=6.6, 2.5 Hz, 1H), 8.2 (s, 1H).

Workup

  1. customthe solvent was evaporated
  2. dissolutionThe residue was dissolved in a mixture of dichloromethane (2.5 mL) and anhydrous TBF (2.5 mL)
  3. stirringThe mixture was shaken overnight
  4. filtrationThe resin was filtered off
  5. customthe solvents were evaporated
  6. customthe crude product was purified on a preparative LC/MS (XTerra Cs column 19×100mm, 0.1 M aqueous NH4Ac/CH3CN)

Sources & evidence

ORD record
ord-6d9c52be7fa04eaabb88db5a54d2c6ca
Source dataset
uspto-grants-2010_01
Patent number
US07645784B2

Reaction notes

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