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

HRID 348333Notes

Reaction equation

HRID 348333 reaction equation
C([O:3][C:4](=[O:24])[C:5]([O:15][C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([CH3:23])[CH:17]=1)([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10](O)=[CH:9][CH:8]=1)C.[CH3:25][C:26]1[O:30][C:29]([C:31]2[CH:36]=[CH:35][C:34]([C:37]3[S:38][CH:39]=[CH:40][CH:41]=3)=[CH:33][CH:32]=2)=[N:28][C:27]=1[CH2:42][CH2:43][O:44]S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[CH3:23][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[CH3:22])[O:15][C:5]([CH3:14])([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:44][CH2:43][CH2:42][C:27]2[N:28]=[C:29]([C:31]3[CH:32]=[CH:33][C:34]([C:37]4[S:38][CH:39]=[CH:40][CH:41]=4)=[CH:35][CH:36]=3)[O:30][C:26]=2[CH3:25])=[CH:11][CH:12]=1)[C:4]([OH:24])=[O:3]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693170842-(3,4-Dimethylphenoxy)-3-(4-hydroxyphenyl)-2-methylpropionic acid ethyl esterHCID 86593515Toluene-4-sulfonic acid 2-(5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl)ethyl ester

Product 1

HCID 102813812-(3,4-Dimethyl-phenoxy)-2-methyl-3-(4-{2-[5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(3,4-dimethylphenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester (0.030 mmol), toluene-4-sulfonic acid 2-(5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl)ethyl ester (0.030 mmol) (see Ex. 3, 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-(3,4-dimethyl-phenoxy)-2-methyl-3-(4-{2-[5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid. 1H NMR (400 MHz, CDCl3) δ 8.16–8.07 (m, 2H), 7.74–7.71 (m, 2H), 7.44–7.35 (m, 2H), 7.18 (d, 2H, J=8.8 Hz), 7.14–7.11 (m, 1H), 7.00 (d, 1H, J=8.4 Hz), 6.83 (d, 2H, J=8.8 Hz), 6.70 (d, 1H, J=2.6 Hz), 6.64 (dd, 1H, J=8.4, 2.6 Hz), 4.31–4.26 (m, 2H), 3.21 and 3.11 (d of Abq, 2H, J=14.0 Hz), 3.12–3.08 (m, 2H), 2.44 (s, 3H), 2.20 (s, 3H), 2.18 (s, 3H), 1.39 (s, 3H). IR (KBr) 3480, 3000, 1716, 1610, 1512, 1250, 1119 cm−1. HRMS (ES+) m/z exact mass calcd for C34H34NO5S 568.2158, found 568.2168.

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-ea97dbe87ba94acd8055a3e14f0174aa
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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