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

HRID 348329Notes

Reaction equation

HRID 348329 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]([OH:13])=[CH:9][CH:8]=1)C.[CH3:29][C:30]1O[C:33]([C:35]2[CH:40]=[CH:39][C:38]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)=[CH:37][CH:36]=2)=[N:32][C:31]=1[CH2:47][CH2:48]OS(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-:66].[Na+]>C(O)C>[C:38]1([C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[CH:37]=[CH:36][C:35]([C:33]2[O:66][C:30]([CH3:29])=[C:31]([CH2:47][CH2:48][O:13][C:10]3[CH:9]=[CH:8][C:7]([CH2:6][C:5]([O:15][C:16]4[CH:17]=[CH:18][C:19]([CH:22]5[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]5)=[CH:20][CH:21]=4)([CH3:14])[C:4]([OH:3])=[O:28])=[CH:12][CH:11]=3)[N:32]=2)=[CH:40][CH:39]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 12966835Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl esterHCID 693147822-(4-Cyclohexylphenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester

Product 1

HCID 101892083-{4-[2-(2-Biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-(4-cyclohexyl-phenoxy)-2-methyl-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) (see Ex. 29, Part C), toluene-4-sulfonic acid 2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethyl ester (0.030 mmol) (see Ex. 1, Part I) 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 3-{4-[2-(2-biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-(4-cyclohexyl-phenoxy)-2-methyl-propionic acid. 1H NMR (400 MHz, CDCl3) δ 8.03 (d, 2H, J=8.60 Hz), 7.66–7.62 (m, 4H), 7.48–7.44 (m, 2H), 7.39–7.36 (m, 1H), 7.19 (d, 3H, J=8.60 Hz), 7.07 (d, 2H, J=8.60 Hz), 6.83 (q, 3H, J=3.52 Hz), 4.13 (t, 2H, J=6.65 Hz), 3.24 (d, 1H, J=13.30 Hz), 3.12 (d, 1H, J=13.30 Hz), 2.99 (t, 2H, J=66.5 Hz), 2.38 (s, 3H), 1.82–1.69 (m, 4H), 1.41 (s, 3H), 1.37–1.22 (m, 6H). MS (ES+) m/z mass calcd for C40H42NO5 616.31, found 616.3.

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-d13bca3715344b3c9fc481429cbda95f
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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