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

HRID 348330Notes

Reaction equation

HRID 348330 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.[C:29]1([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH:34]=[CH:33][CH:32]=[C:31]([C:35]2O[C:37]([CH3:53])=[C:38]([CH2:40][CH2:41]OS(C3C=CC(C)=CC=3)(=O)=O)[N:39]=2)[CH:30]=1.C([O-])([O-])=O.[K+].[K+].[OH-:66].[Na+]>C(O)C>[C:29]1([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[CH:34]=[CH:33][CH:32]=[C:31]([C:35]2[O:66][C:37]([CH3:53])=[C:38]([CH2:40][CH2:41][O:13][C:10]3[CH:9]=[CH:8][C:7]([CH2:6][C:5]([O:15][C:16]4[CH:21]=[CH:20][C:19]([CH:22]5[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]5)=[CH:18][CH:17]=4)([CH3:14])[C:4]([OH:3])=[O:28])=[CH:12][CH:11]=3)[N:39]=2)[CH:30]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 58979436Toluene-4-sulfonic acid 2-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethyl esterHCID 693147822-(4-Cyclohexylphenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester

Product 1

HCID 101217553-{4-[2-(2-Biphenyl-3-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-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethyl ester (0.030 mmol) (see Ex. 2, Part P) 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-3-yl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-(4-cyclohexyl-phenoxy)-2-methyl-propionic acid. 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H), 7.96–7.93 (m, 1H), 7.64 (t, 3H, J=8.21 Hz), 7.50–7.43 (m, 3H), 7.37 (d, 1H, J=8.21 Hz), 7.18 (d, 2H, J=8.60 Hz), 7.07 (d, 2H, J=8.60 Hz), 6.83 (dd, 4H, J=8.60 Hz, 5.47 Hz), 4.22 (t, 2H, J=6.65 Hz), 3.26 (d, 1H, J=14.08 Hz), 3.16 (d, 1H, J=14.08 Hz), 2.99 (t, 2H, J=6.65 Hz), 2.39 (s, 3H), 2.17 (s, 1H), 1.81 (d, 4H, J=9.78 Hz), 1.41 (s, 3H), 1.37–1.22 (m, 5H). 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-713ed9843e6f45f191c42dedd87282f6
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

Loading…