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

HRID 417152Notes

Reaction equation

HRID 417152 reaction equation
C(N(N=O)[C:9](=[O:34])[CH:10]([N:16]1[C:20]2[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:19]=2[N:18]=[C:17]1[C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=1)[CH:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1)C1C=CC=CC=1.[OH2:37].[OH-].[Li+].OO.Cl>O1CCCC1.O.C(OCC)(=O)C>[Cl:33][C:30]1[CH:29]=[CH:28][C:27]([C:17]2[N:16]([CH:10]([CH:11]3[CH2:12][CH2:13][CH2:14][CH2:15]3)[C:9]([OH:37])=[O:34])[C:20]3[CH:21]=[C:22]([F:26])[C:23]([F:25])=[CH:24][C:19]=3[N:18]=2)=[CH:32][CH:31]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 168937Lithium hydroxide, monohydrateHCID 86639902N-benzyl-N-nitroso-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-acetamide

Product 1

HCID 66619513[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclopentyl-acetic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent3×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a ice-cold suspension of 8.10 g (15.91 mmol) N-benzyl-N-nitroso-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclopentyl-acetamide in 45 ml tetrahydrofuran and ml water were added dropwise over 30 min. a solution of 6.68 g (159 mmol) lithium hydroxide monohydrate in 32.50 ml (318 mmol) 30% hydrogen peroxide solution and 15 ml water. After stirring for 4.5 h at room temperature, 150 ml water and 100 ml ethyl acetate were added and the pH adjusted to 1 using 25% aqueous hydrochloric acid. The phases were separated and the aqueous phase extracted three times with ethyl acetate. The combined organic layers were washed with saturated aqueous sodium bicarbonate solution and brine, then dried over magnesium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane:ethyl acetate:methanole (100:0:0 to 0:100:0 to 0:85:15). Off-white solid (55%). MS (Turbo Spray): m/z=391.1 [M+H].

Workup

  1. customThe phases were separated
  2. extractionthe aqueous phase extracted three times with ethyl acetate
  3. washThe combined organic layers were washed with saturated aqueous sodium bicarbonate solution and brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a gradient of heptane

Sources & evidence

ORD record
ord-1bf725b02daf474ca101f50e46cbcdeb
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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