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

HRID 348322Notes

Reaction equation

HRID 348322 reaction equation
C([O:3][C:4](=[O:23])[C:5]([O:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)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>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([O:15][C:5]([CH3:14])([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([O:13][CH2:42][CH2:41][C:26]3[N:27]=[C:28]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([C:36]5[S:37][CH:38]=[CH:39][CH:40]=5)[CH:31]=4)[O:29][C:25]=3[CH3:24])=[CH:11][CH:12]=2)[C:4]([OH:3])=[O:23])=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693158912-(4-Chlorophenoxy)-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 101207962-(4-Chlorophenoxy)-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-chlorophenoxy)-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-chlorophenoxy)-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 8.23 (s, 1H), 8.87 (d, 1H, J=8.21 Hz), 7.69–7.67 (m, 1H), 7.46 (d, 1H, J=8.21 Hz), 7.42 (dd, 1H, J=3.52 Hz, 2.74 Hz), 7.32 (dd, 1H, J=5.08 Hz, 2.74 Hz), 7.19–7.15 (m, 3H), 7.18 (dd, 2H, J=6.26 Hz, 2.74 Hz), 6.82 (dd, 4H, J=8.60 Hz, 2.74 Hz), 4.22 (t, 2H, J=6.26 Hz), 3.24 (d, 1H, J=14.08 Hz), 3.10 (d, 1H, J=14.08 Hz), 3.05 (t, 2H, J=6.26 Hz), 2.42 (s, 3H), 1.40 (s, 3H). MS (ES+) m/z mass calcd for C32H29ClNO5S 574.15, found 574.2.

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-5ffa71d46c764eb99b539da1552e59a5
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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