2-Chloro-4-[[[[1-[(1,1-dimethylethoxy)carbonyl]benzimidazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester → HCID 178522789, compound

HRID 2270810Notes

Reaction equation

HRID 2270810 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[C:24]3[N:23]=[CH:22][N:21](C(OC(C)(C)C)=O)[C:20]=3[CH:19]=[CH:18][CH:17]=2)=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5]>CO.[OH-].[Li+]>[Cl:1][C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][C:16]2[C:24]3[NH:23][CH:22]=[N:21][C:20]=3[CH:19]=[CH:18][CH:17]=2)=[O:13])[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

4

Reactant 1

HCID 865851472-Chloro-4-[[[[1-[(1,1-dimethylethoxy)carbonyl]benzimidazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester

Product 1

HCID 178522789HCID 178522789, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 3939Lithium HydroxideSolvent

Procedure

A mixture of 4-(azidomethyl)benzimidazole-1-carboxylic acid, 1,1-dimethylethyl ester (Example 13; 1.40, 5.1 mmol), 1-[[3-chloro-4-(methoxycarbonyl)benzoyl]oxy]-2,5-pyrrolidinedione (Example 5; 1.62 g, 5.2 mmol), and 10% palladium on charcoal (210 mg) in methanol (40 mL) and benzene (2 mL) was hydrogenated at atmospheric pressure for 105 min and then filtered through Celite. Tlc indicated that the reaction was not complete so more 10% palladium on charcoal (210 mg) was added and the mixture was hydrogenated at atmospheric pressure for 3 h and then shaken at 50 psi of hydrogen for 3 h. The reaction mixture was allowed to stand under hydrogen for 12 h, then filtered through Celite, evaporated, and chromatographed (20-100% ethyl acetate/hexanes) to give 2-chloro-4-[[[[1-[(1,1-dimethylethoxy)carbonyl]benzimidazol-4-yl]methyl]amino]carbonyl]benzoic acid, methyl ester (1.50 g, 66%). A solution of the ester (1.45 g, 3.3 mmol) in methanol (15 mL) and 3 M lithium hydroxide solution (5.5 mL) was stirred at room temperature overnight. A white solid was filtered off and discarded. The filtrate was evaporated to dryness. Water and 1 M HCl (16.6 mL) were added, and the mixture was filtered and washed with water to give 2-chloro-4-[[[(benzimidazol-4-yl)methyl]amino]carbonyl]-benzoic acid (925 mg, 86%).

Workup

  1. filtrationA white solid was filtered off
  2. customThe filtrate was evaporated to dryness
  3. additionWater and 1 M HCl (16.6 mL) were added
  4. filtrationthe mixture was filtered
  5. washwashed with water

Sources & evidence

ORD record
ord-a1c51fc302864d45a5293923d2af56e0
Source dataset
uspto-grants-2001_12
Patent number
US06331640B1

Reaction notes

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