Hydrochloric Acid → 4-(5-Amino-1-methyl-1H-benzoimidazol-2-yl)-butyric acid methyl ester hydrochloride

HRID 1967485Notes

Reaction equation

HRID 1967485 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][CH2:6][C:7](=O)[N:8]([C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-])=O)=[CH:12][C:11]=1[N+:19]([O-])=O)[CH3:9].[ClH:24]>[Pd].CO>[ClH:24].[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][CH2:6][C:7]1[N:8]([CH3:9])[C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][C:11]=2[N:19]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 583828074-[(2,4-Dinitro-phenyl)-methyl-carbamoyl]-butyric acid methyl ester

Product 1

HCID 468993894-(5-Amino-1-methyl-1H-benzoimidazol-2-yl)-butyric acid methyl ester hydrochlorideYield 99%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

A one liter Buchi reactor was charged with 42.7 g (131.4 mmol, 1.0 equiv.) of 4-[(2,4-dinitro-phenyl)-methyl-carbamoyl]-butyric acid methyl ester, 20 g of 10% palladium on carbon (4.7% weight ratio palladium vs. starting material), and 650 mL of methanol at ambient temperature. The resulting mixture was subjected to hydrogenation at 40 psi overnight, about 18 hours. HPLC indicated that the reaction was complete in about 6-7 hours (HPLC Method B). The reaction mixture was filtered through a thin layer of Celite® 540. To the filtrate was added 12 mL of concentrated hydrochloric acid (1.1 equiv.). The resulting mixture was stirred under reflux for 3.5 hours. Solvent was removed under reduced pressure, and the solids were slurried in 1800 mL of 2 vol % of Methanol/Tert-butyl methyl ether at room temperature overnight. The solids were collected by filtration. The product was dried at 45-50° C. overnight under vacuum to afford a coffee-colored solid (36.8 g, 99% yield) with a purity of 99 Area % by HPLC analysis (HPLC Method B).

Workup

  1. customat ambient temperature
  2. customwas subjected to hydrogenation at 40 psi overnight, about 18 hours
  3. filtrationThe reaction mixture was filtered through a thin layer of Celite® 540
  4. temperatureunder reflux for 3.5 hours
  5. customSolvent was removed under reduced pressure
  6. customat room temperature
  7. customovernight
  8. filtrationThe solids were collected by filtration
  9. customThe product was dried at 45-50° C. overnight under vacuum

Sources & evidence

ORD record
ord-4ccf48678d3c4ae3abf15179061c443d
Source dataset
uspto-grants-2013_04
Patent number
US08420829B2

Reaction notes

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