Hydrochloric Acid → 3-(2-Methyl-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethoxymethyl}-phenyl)-propionic Acid

HRID 860684Notes

Reaction equation

HRID 860684 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[O:5][C:6]=1[CH:7]([OH:9])[CH3:8].[H-].[Na+].C[O:23][C:24](=[O:36])[CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([CH2:33]I)=[CH:29][C:28]=1[CH3:35].Cl>[OH-].[Na+].CN(C)C=O>[CH3:35][C:28]1[CH:29]=[C:30]([CH2:33][O:9][CH:7]([C:6]2[O:5][C:4]([C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=3)=[N:3][C:2]=2[CH3:1])[CH3:8])[CH:31]=[CH:32][C:27]=1[CH2:26][CH2:25][C:24]([OH:36])=[O:23]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 574319743-(4-Iodomethyl-2-methyl-phenyl)-propionic acid methyl esterHCID 587657681-[4-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethanol

Product 1

HCID 695893723-(2-Methyl-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethoxymethyl}-phenyl)-propionic Acid

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolvent

Procedure

A mixture of 1-[4-Methyl-2-(4-trifluoromethyl-phenyl)-oxazol-5-yl]-ethanol (0.132 g, 0.487 mmol), sodium hydride (0.05 g, 1.25 mmol) and N,N-dimethyl formamide (5 mL) is stirred at room temperature. 3-(4-Iodomethyl-2-methyl-phenyl)-propionic acid methyl ester (0.17 g, 0.535 mmol) is added and the mixture is heated to 65 deg C., 2 hr. The reaction is cooled to room temperature and diluted with aqueous sodium hydroxide (10 mL, 5M) and stirred 1 hr. The pH is adjusted with aqueous hydrochloric acid until pH is 2–3. The product is extracted into ethyl acetate (3×25 mL). The combined extracts are dried over anhydrous magnesium sulfate, filtered and concentrated. The residue is purified via silica chromatography eluting with 7:3 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate to afford the title compound as a white solid, 0.027 g, 12%. MS M++1 448. The structure is confirmed by 1H NMR spectroscopy.

Workup

  1. temperaturethe mixture is heated to 65 deg C
  2. custom2 hr
  3. temperatureThe reaction is cooled to room temperature
  4. stirringstirred 1 hr
  5. extractionThe product is extracted into ethyl acetate (3×25 mL)
  6. dry with materialThe combined extracts are dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue is purified via silica chromatography
  10. washeluting with 7:3 hexanes

Sources & evidence

ORD record
ord-af2a6d59a856413fb433868be0ba8b82
Source dataset
uspto-grants-2006_12
Patent number
US07153878B2

Reaction notes

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