Hydrochloric Acid → 4-{3-Cyclohexyl-3-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-propyl}-benzoic acid

HRID 417167Notes

Reaction equation

HRID 417167 reaction equation
C[O:2][C:3](=[O:40])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][CH:12]([CH:34]2[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]2)[N:13]2[C:17]3[CH:18]=[C:19]([F:23])[C:20]([F:22])=[CH:21][C:16]=3[N:15]=[C:14]2[C:24]2[C:25]([O:32][CH3:33])=[N:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)=[CH:6][CH:5]=1.O.O.[OH-].[Li+].Cl>O1CCOCC1.C(OCC)(=O)C>[CH:34]1([CH:12]([N:13]2[C:17]3[CH:18]=[C:19]([F:23])[C:20]([F:22])=[CH:21][C:16]=3[N:15]=[C:14]2[C:24]2[C:25]([O:32][CH3:33])=[N:26][C:27]([O:30][CH3:31])=[CH:28][CH:29]=2)[CH2:11][CH2:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:40])=[O:2])=[CH:5][CH:6]=2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 666194954-{3-Cyclohexyl-3-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-propyl}-benzoic acid methyl ester

Product 1

HCID 461834944-{3-Cyclohexyl-3-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-propyl}-benzoic acidYield 78%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 180 mg (0.327 mmol) 4-{3-cyclohexyl-3-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-propyl}-benzoic acid methyl ester in 3 ml dioxane was added 3 ml water and 41 mg (0.98 mmol) lithium hydroxide monohydrate. The reaction mixture was stirred for 4 h at 100° C. and then poured on 30 ml aqueous 1M hydrochloric acid and 30 ml ethyl acetate. The aqueous layer was extracted a second time with 30 ml ethyl acetate. The combined organic layers were washed with 30 ml brine, dried over magnesium sulfate, filtered and concentrated under vacuum. The residue was purified by preparative HPLC (phenomenex gemini column) eluting with a gradient of acetonitril:water (50:50 to 95:5) to give the title compound as a light yellow solid (78%). MS (Turbo Spray): m/z=536.236 [M+H].

Workup

  1. extractionThe aqueous layer was extracted a second time with 30 ml ethyl acetate
  2. washThe combined organic layers were washed with 30 ml brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified by preparative HPLC (phenomenex gemini column)
  7. washeluting with a gradient of acetonitril:water (50:50 to 95:5)

Sources & evidence

ORD record
ord-1c7e93f62ea5470f826faa6394b11c98
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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