Methyl 4-aminobenzoate → HCID 59850259, compound

HRID 545303Notes

Reaction equation

HRID 545303 reaction equation
F[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[NH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=1.CC(C)([O-])C.[K+]>CS(C)=O>[C:6]([C:5]1[CH:8]=[CH:9][C:2]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:22][CH:23]=2)=[C:3]([N+:10]([O-:12])=[O:11])[CH:4]=1)#[N:7]

Participants

5

Reactant 3

HCID 12082Methyl 4-aminobenzoateHCID 27746544-Fluoro-3-nitrobenzonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 59850259HCID 59850259, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of 4-fluoro-3-nitrobenzonitrile (2.00 g, 12.04 mmol) and methyl 4-aminobenzoate (1.94 g, 12.83 mmol) in DMSO (40 mL) was cooled in an ice-bath and potassium tert-butoxide (2.96 g, 26.38 mmol) was added over 15 min. The reaction mixture was allowed to stir at room temperature for 3 h. The reaction mixture was quenched with ice; the solid product was recovered by filtration, washed with water and dried under vacuum to afford 2.4 g (68%) of methyl 4-[(4-cyano-2-nitrophenyl)amino]benzoate. To a solution of methyl 4-[(4-cyano-2-nitrophenyl)amino]benzoate (0.2 g, 0.67 mmol) in ethanol (4 mL) was added palladium on carbon (10 wt. %, 0.06 g) and hydrazine hydrate (0.13 g, 2.60 mmol) and the reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature, filtered through celite, and the solvent evaporated. The residue was dissolved in ethyl acetate, washed with water, dried (Na2SO4) and evaporated under reduced pressure to afford a crude oil. To a solution of the oil in trimethyl orthoformate (10 mL) was added formic acid (0.31 g, 7.7 mmol, 3 eq) and the reaction mixture was heated at reflux for 2 h. The reaction mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The residue was partitioned between water and ethyl acetate and the organic layer was dried (Na2SO4) and evaporated to afford a crude solid. Purification by flash column chromatography (silica, CHCl3/MeOH 98:2) afforded 0.12 g (63%) of methyl 4-(5-cyano-1H-benzimidazol-1-yl)benzoate. MS [M+H] 277.

Workup

  1. temperaturewas cooled in an ice-bath
  2. customThe reaction mixture was quenched with ice
  3. filtrationthe solid product was recovered by filtration
  4. washwashed with water
  5. customdried under vacuum

Sources & evidence

ORD record
ord-cbd5740808e540b2bbb33f666a46ac70
Source dataset
uspto-grants-2011_05
Patent number
US07935719B2

Reaction notes

Loading…