Potassium Carbonate → 2-(4-{2-[5-Methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-butyric acid

HRID 348349Notes

Reaction equation

HRID 348349 reaction equation
C([O:3][C:4](=[O:23])[C:5]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1)([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:6][CH3:7])C.[CH3:24][C:25]1[O:29][C:28]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]3[S:37][CH:38]=[CH:39][CH:40]=3)[CH:31]=2)=[N:27][C:26]=1[CH2:41][CH2:42]OS(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[CH3:24][C:25]1[O:29][C:28]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([C:36]3[S:37][CH:38]=[CH:39][CH:40]=3)[CH:31]=2)=[N:27][C:26]=1[CH2:41][CH2:42][O:22][C:19]1[CH:18]=[CH:17][C:16]([CH2:15][C:5]([O:8][C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)([CH2:6][CH3:7])[C:4]([OH:3])=[O:23])=[CH:21][CH:20]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 69320315HCID 69320315, compoundHCID 86593517Toluene-4-sulfonic acid 2-[5-methyl-2-(3-thiophen-2-ylphenyl)oxazol-4-yl]ethyl ester

Product 1

HCID 102809322-(4-{2-[5-Methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-butyric acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(4-hydroxybenzyl)-2-phenoxybutyric acid ethyl ester (0.030 mmol) (see Ex. 40, Part C), toluene-4-sulfonic acid 2-[5-methyl-2-(3-thiophen-2-ylphenyl)oxazol-4-yl]ethyl ester (0.030 mmol) (see Ex. 5, Part B) and 325 mesh K2CO3 (0.084 g, 0.60 mmol) in ethanol (2 mL) was heated to reflux for 24 h under N2. Aqueous 5N NaOH (0.5 mL) and additional ethanol (1 mL) was added to the reaction mixture and it was heated at reflux for an additional 2 h. The reaction was cooled and the solvent removed in vacuo. The residue was acidified with aqueous 1 N HCl (5 mL), extracted with water and CH2Cl2 and the organic layer dried by passing it through a Varian Chem Elut 1003 cartridge. The solvent was removed in vacuo to give 2-(4-{2-[5-methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-butyric acid. 1H NMR (400 MHz, CDCl3) δ 8.22–8.21 (m, 1H), 7.89–7.85 (m, 1H), 7.66–7.62 (m, 1H), 7.45–7.40 (m, 2H), 7.32–7.25 (m, 3H), 7.11–6.97 (m, 6H), 6.77 (d, 2H, J=8.4 Hz), 4.20 (t, 2H, J=6.4 Hz), 3.29 (s, 2H), 2.98 (t, 2H, J=6.4 Hz), 2.39 (s, 3H), 2.14 (qd, 1H, J=14.6, 7.6 Hz), 2.07 (qd, 1H, J=14.6, 7.6 Hz), 0.91 (t, 3H, J=7.6 Hz).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 h under N2
  3. temperaturewas heated
  4. temperatureat reflux for an additional 2 h
  5. temperatureThe reaction was cooled
  6. customthe solvent removed in vacuo
  7. extractionextracted with water and CH2Cl2
  8. customthe organic layer dried
  9. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-ba29fefa91f74aff878d5746d807ae58
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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