Potassium Carbonate → 2-Methyl-3-(4-{2-[5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-2-m-tolyloxy-propionic acid

HRID 348362Notes

Reaction equation

HRID 348362 reaction equation
C([O:3][C:4](=[O:23])[C:5]([O:15][C:16]1[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=1)([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10](O)=[CH:9][CH:8]=1)C.[CH3:24][C:25]1[O:29][C:28]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[S:37][CH:38]=[CH:39][CH:40]=3)=[CH:32][CH:31]=2)=[N:27][C:26]=1[CH2:41][CH2:42][O:43]S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[CH3:14][C:5]([O:15][C:16]1[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=1)([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([O:43][CH2:42][CH2:41][C:26]2[N:27]=[C:28]([C:30]3[CH:31]=[CH:32][C:33]([C:36]4[S:37][CH:38]=[CH:39][CH:40]=4)=[CH:34][CH:35]=3)[O:29][C:25]=2[CH3:24])=[CH:9][CH:8]=1)[C:4]([OH:23])=[O:3]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693161843-(4-Hydroxyphenyl)-2-methyl-2-m-tolyloxy-propionic acid ethyl esterHCID 86593515Toluene-4-sulfonic acid 2-(5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl)ethyl ester

Product 1

HCID 102310972-Methyl-3-(4-{2-[5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-2-m-tolyloxy-propionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(m-tolyloxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester (0.095 g, 0.030 mmol) (see Ex. 48, Part C), toluene-4-sulfonic acid 2-(5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl)ethyl ester (0.030 mmol) 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-methyl-3-(4-{2-[5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-2-m-tolyloxy-propionic acid. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, 2H, J=8.60 Hz), 7.68 (d, 2H, J=8.60 Hz), 7.40 (d, 1H, J=3.52 Hz), 7.34 (d, 1H, J=4.69 Hz), 7.18 (d, 2H, J=8.21 Hz), 7.15–7.09 (m, 2H), 6.87–6.82 (m, 3H), 6.72–6.69 (m, 2H), 4.22 (t, 2H, J=6.26 Hz), 3.23 (d, 1H, J=14.08 Hz), 3.13 (d, 1H, J=14.08 Hz), 3.03 (t, 2H, J=6.26 Hz) 2.41 (s, 3H), 2.29 (s, 3H), 1.42 (s, 3H); HRMS (ES+) m/z exact mass calcd for C33H32NO5S 554.2001, found 554.2022.

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-0a126265c594402f9aff5782f38798cb
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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