Hydrochloric Acid → [2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopropyl-acetic acid

HRID 417157Notes

Reaction equation

HRID 417157 reaction equation
C(N(N=O)[C:9](=[O:32])[CH:10]([N:14]1[C:18]2[CH:19]=[C:20]([F:24])[C:21]([F:23])=[CH:22][C:17]=2[N:16]=[C:15]1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)[CH:11]1[CH2:13][CH2:12]1)C1C=CC=CC=1.[OH2:35].[OH-].[Li+].OO.Cl>O1CCCC1.O.C(O)(=O)C>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([C:15]2[N:14]([CH:10]([CH:11]3[CH2:13][CH2:12]3)[C:9]([OH:32])=[O:35])[C:18]3[CH:19]=[C:20]([F:24])[C:21]([F:23])=[CH:22][C:17]=3[N:16]=2)=[CH:26][CH:27]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 86639903N-benzyl-N-nitroso-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-acetamide

Product 1

HCID 66619353[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopropyl-acetic acidYield 56%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a ice-cold suspension of 10.15 g (21.11 mmol) N-benzyl-N-nitroso-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopropyl-acetamide in 60 ml tetrahydrofuran and 15 ml water were added dropwise over 30 min. a solution of 8.86 g (211 mmol) lithium hydroxide monohydrate in 43.1 ml (422 mmol) hydrogen peroxide 30% solution and 30 ml water. After stirring for 2.25 h at room temperature the pH was adjusted to 3 using 70 ml acetic acid and 25% aqueous hydrochloric acid. The resulting light yellow solution was extracted three times with ethyl acetate. The organic layers were washed with water, aqueous saturated sodium bicarbonate solution and brine. After drying over magnesium sulfate and filtration, the solution was evaporated until a suspension formed. This suspension was filtered and washed with ethyl acetate to give the compound as a white solid (56%). MS (Turbo Spray): m/z=363.2 [M+H].

Workup

  1. extractionThe resulting light yellow solution was extracted three times with ethyl acetate
  2. washThe organic layers were washed with water, aqueous saturated sodium bicarbonate solution and brine
  3. dry with materialAfter drying over magnesium sulfate and filtration
  4. customthe solution was evaporated until a suspension
  5. customformed
  6. filtrationThis suspension was filtered
  7. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-c0cfd41417dd433abf9a6ef947660c8b
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

Loading…