Lithium hydroxide, monohydrate → [2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid

HRID 417162Notes

Reaction equation

HRID 417162 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)[C:14](C)([O:16]C3C=CC(C4NN=NN=4)=CC=3)C)[C:11]3[CH:35]=[C:36]([F:40])[C:37]([F:39])=[CH:38][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[OH2:41].[OH-].[Li+]>O1CCOCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:29]3[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]3)[C:14]([OH:41])=[O:16])[C:11]3[CH:35]=[C:36]([F:40])[C:37]([F:39])=[CH:38][C:10]=3[N:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 178458272HCID 178458272, compound2×

Product 1

HCID 66619321[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To the solution of 0.17 g (0.469 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid ethyl ester (Example 1, intermediate b) in 4 ml dioxan and 2 ml water, 34 mg (1.42 mmol) lithium hydroxide monohydrate were added and the reaction was stirred at reflux temperature for 2 h. After cooling to room temperature the solution was partially evaporated, diluted with 2 ml water and the pH was adjusted to 1-2 with 1M aqueous hydrochloric acid. The resulting suspension was stirred for 30 min. and then filtered. The filter cake was thoroughly washed with water and dried under high vacuum. Colorless solid (83%). MS (Turbo Spray): m/z=333.3 [M−H].

Workup

  1. temperatureat reflux temperature for 2 h
  2. customwas partially evaporated
  3. additiondiluted with 2 ml water
  4. stirringThe resulting suspension was stirred for 30 min.
  5. filtrationfiltered
  6. washThe filter cake was thoroughly washed with water
  7. customdried under high vacuum

Sources & evidence

ORD record
ord-1783f87210654084835a434726a3517b
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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