Hydrochloric Acid → 3-chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)methoxy)-5-fluorobenzoic acid

HRID 83923Notes

Reaction equation

HRID 83923 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([F:37])[C:11]=1[O:12][CH2:13][C:14]1[N:15]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:16]([C:19]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)([CH3:21])[CH3:20])=[CH:17][N:18]=1)[C:5]([O:7]C)=[O:6].[OH-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([F:37])[C:11]=1[O:12][CH2:13][C:14]1[N:15]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[C:16]([C:19]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[C:24]([Cl:29])[CH:23]=2)([CH3:21])[CH3:20])=[CH:17][N:18]=1)[C:5]([OH:7])=[O:6]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66740309methyl 3-chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)methoxy)-5-fluorobenzoate

Product 1

HCID 667402383-chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)methoxy)-5-fluorobenzoic acidYield 39%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of methyl 3-chloro-4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)methoxy)-5-fluorobenzoate (120 mg, 0.21 mmol) and 2N NaOH (0.31 mL, 0.63 mmol) in MeOH (3 mL) was heated 3 h at 65° C. After cooling, the reaction was neutralized to pH 3 with 3N HCl, concentrated under reduced pressure, diluted with water, and then extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude material was purified by HPLC (MeCN/H2O, 10-99%) to give the title compound as an off-white solid (45 mg, 39%). MS (EI): 553.5 [M+H]+.

Workup

  1. temperatureAfter cooling
  2. concentrationconcentrated under reduced pressure
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by HPLC (MeCN/H2O, 10-99%)

Sources & evidence

ORD record
ord-c989eabff709493cb71096a75442fa26
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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