Hydrochloric Acid → 6-[2-Chloro-4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylic acid

HRID 646005Notes

Reaction equation

HRID 646005 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[C:11]([C:18]3[C:23]([Cl:24])=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:25])=[N:12][O:13][C:14]=2[CH:15]([CH3:17])[CH3:16])[CH:5]=[CH:4][C:3]=1[C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32]([C:36]([O:38]C)=[O:37])=[CH:31][CH:30]=[CH:29]2.C1COCC1.[OH-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][C:10]2[C:11]([C:18]3[C:19]([Cl:25])=[CH:20][CH:21]=[CH:22][C:23]=3[Cl:24])=[N:12][O:13][C:14]=2[CH:15]([CH3:17])[CH3:16])[CH:5]=[CH:4][C:3]=1[C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][CH:35]=1)[C:32]([C:36]([OH:38])=[O:37])=[CH:31][CH:30]=[CH:29]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59264865Methyl 6-[2-chloro-4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylate

Product 1

HCID 247390176-[2-Chloro-4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylic acidYield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

A solution of methyl 6-[2-chloro-4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylate (0.36 g, 0.62 mmol), 6.5 mL of THF, 3.5 mL of methanol and 1.3 mL of 1 N NaOH was stirred for 18 h at rt. The reaction mixture was heated to 65° C. for 2 hours. The solution was allowed to cool to room temperature and the pH was adjusted with 1N HCl. The solution was concentrated and the residue was extracted with ethyl acetate. The organic layer was dried with MgSO4, filtered, and the filtrate was concentrated to give the crude product as oil. The crude material was purified by flash chromatography (silica gel, gradient hexane to hexanes/ethyl acetate, 1:1) to afford the title compound as a white foam (0.15 g, 67%). 1H NMR (DMSO-d6): δ 13.13 (s, 1H), 8.87 (d, J=9 Hz, 1H), 8.19-8.14 (m, 2H), 7.97 (m, 1H), 7.64-7.53 (m, 5H), 7.36 (d, J=9 Hz, 1H), 7.04 (m, 1H), 6.86-6.84 (m, 1H), 4.92 (s, 2H), 3.48 (septet, J=7 Hz, 1H), 1.33 (d, J=7 Hz, 6 H). HRMS C30H22Cl3NO4 m/z 566.0693 (M+H)+Cal; 566.0687 (M+H)+Obs.

Workup

  1. temperatureto cool to room temperature
  2. concentrationThe solution was concentrated
  3. extractionthe residue was extracted with ethyl acetate
  4. dry with materialThe organic layer was dried with MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customto give the crude product as oil
  8. customThe crude material was purified by flash chromatography (silica gel, gradient hexane to hexanes/ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-3d1af5258bbe449992694b38aab4dbd4
Source dataset
uspto-grants-2010_04
Patent number
US07705028B2

Reaction notes

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