Sodium Hydroxide → 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-(4-fluorophenyl)-1H-imidazol-2-yl)ethyl)-5-fluorobenzoic acid

HRID 1627325Notes

Reaction equation

HRID 1627325 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([F:39])[C:12]=1[CH2:13][CH2:14][C:15]1[N:16]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[C:17]([C:20]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([O:30][CH3:31])[CH:24]=2)([CH3:22])[CH3:21])=[CH:18][N:19]=1)[C:5]([O:7]CC)=[O:6].[OH-].[Na+]>CO.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([F:39])[C:12]=1[CH2:13][CH2:14][C:15]1[N:16]([C:32]2[CH:33]=[CH:34][C:35]([F:38])=[CH:36][CH:37]=2)[C:17]([C:20]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([O:30][CH3:31])[CH:24]=2)([CH3:22])[CH3:21])=[CH:18][N:19]=1)[C:5]([OH:7])=[O:6]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 66739864ethyl 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)ethyl)-5-fluorobenzoate

Product 1

HCID 667403173-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-(4-fluorophenyl)-1H-imidazol-2-yl)ethyl)-5-fluorobenzoic acidYield 81%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of ethyl 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)ethyl)-5-fluorobenzoate (151 mg, 0.263 mmol) in MeOH (1.0 mL) was added dropwise a 2N solution of NaOH in H2O (0.5 mL). After stirring 1 h, the reaction mixture was concentrated under reduced pressure, diluted with H2O (1.5 mL), neutralized with 1N HCl and then extracted with DCM (10 mL×2). The combined extracts were dried (MgSO4), filtered and concentrated to give the title compound (116 mg, 81%) as gray solid. 1H NMR (400 MHz, DMSO) δ 7.69 (s, 1H), 7.57 (d, J=9.6 Hz, 1H), 7.27-7.17 (m, 2H), 7.05 (d, J=8.6 Hz, 1H), 7.03 (d, J=8.6 Hz, 1H), 6.69 (dd, J=8.6, 4.8 Hz, 2H), 6.54 (s, 1H), 6.53-6.48 (m, 1H), 3.69 (s, 3H), 2.94 (t, J=7.2 Hz, 2H), 2.57 (t, J=7.2 Hz, 2H), 1.48 (s, 6H).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. additiondiluted with H2O (1.5 mL)
  3. extractionextracted with DCM (10 mL×2)
  4. dry with materialThe combined extracts were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-cb02e01e611f4ae28297b0d68210f842
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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