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

HRID 348328Notes

Reaction equation

HRID 348328 reaction equation
C([O:3][C:4](=[O:28])[C:5]([O:15][C:16]1[CH:21]=[CH:20][C:19]([CH:22]2[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1)([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10](O)=[CH:9][CH:8]=1)C.[CH3:29][C:30]1[O:34][C:33]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([C:41]3[S:42][CH:43]=[CH:44][CH:45]=3)[CH:36]=2)=[N:32][C:31]=1[CH2:46][CH2:47][O:48]S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[CH:22]1([C:19]2[CH:20]=[CH:21][C:16]([O:15][C:5]([CH3:14])([CH2:6][C:7]3[CH:8]=[CH:9][C:10]([O:48][CH2:47][CH2:46][C:31]4[N:32]=[C:33]([C:35]5[CH:40]=[CH:39][CH:38]=[C:37]([C:41]6[S:42][CH:43]=[CH:44][CH:45]=6)[CH:36]=5)[O:34][C:30]=4[CH3:29])=[CH:11][CH:12]=3)[C:4]([OH:28])=[O:3])=[CH:17][CH:18]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693147822-(4-Cyclohexylphenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl esterHCID 86593517Toluene-4-sulfonic acid 2-[5-methyl-2-(3-thiophen-2-ylphenyl)oxazol-4-yl]ethyl ester

Product 1

HCID 102328142-(4-Cyclohexyl-phenoxy)-2-methyl-3-(4-{2-[5-methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(4-cyclohexylphenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester (0.030 mmol), 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-cyclohexyl-phenoxy)-2-methyl-3-(4-{2-[5-methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid. 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.88 (d, 1H, J=7.82 Hz), 7.64 (d, 1H, J=7.82 Hz), 7.43 (d, 1H, J=7.82 Hz), 7.41 (dd, 1H, J=3.52 Hz, 1.17 Hz), 7.31 (dd, 1H, J=3.91 Hz, 1.17 Hz), 7.19 (d, 2H, J=8.60 Hz), 7.10–7.06 (m, 3H), 6.84 (d, 2H, J=7.04 Hz), 6.82 (d, 2H, J=8.21 Hz), 4.23 (t, 2H, J=6.65 Hz), 3.22 (d, 1H, J=14.08 Hz), 3.13 (d, 1H, J=14.08 Hz), 2.99 (t, 2H, J=6.65 Hz), 2.39 (s, 3H), 1.81 (d, 5H, J=8.60 Hz), 1.40 (s, 3H), 1.38–1.32 (m, 5H). MS (ES+) m/z mass calcd C38H40NO5S 622.26, found 622.3.

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-7aead9268a0b489c803771d203e719a4
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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