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

HRID 348360Notes

Reaction equation

HRID 348360 reaction equation
C([O:3][C:4](=[O:23])[C:5]([O:15][C:16]1[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=1)([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)C.[C:24]1([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[O:31][C:32]([CH3:48])=[C:33]([CH2:35][CH2:36]OS(C3C=CC(C)=CC=3)(=O)=O)[N:34]=2)[CH:25]=1.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[C:24]1([C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][CH:54]=2)[CH:29]=[CH:28][CH:27]=[C:26]([C:30]2[O:31][C:32]([CH3:48])=[C:33]([CH2:35][CH2:36][O:13][C:10]3[CH:11]=[CH:12][C:7]([CH2:6][C:5]([CH3:14])([O:15][C:16]4[CH:17]=[C:18]([CH3:22])[CH:19]=[CH:20][CH:21]=4)[C:4]([OH:3])=[O:23])=[CH:8][CH:9]=3)[N:34]=2)[CH:25]=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 693161843-(4-Hydroxyphenyl)-2-methyl-2-m-tolyloxy-propionic acid ethyl ester

Product 1

HCID 103026663-(4-[2-(2-Biphenyl-3-yl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-methyl-2-m-tolyloxy-propionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(m-tolyloxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester (0.095 g, 0.030 mmol), toluene-4-sulfonic acid 2-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethyl ester (0.030 mmol) 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-methyl-2-m-tolyloxy-propionic acid. 1H NMR (400 MHz, CDCl3) δ 8.18–8.17 (m, 1H), 7.92 (d, 1H, J=7.04 Hz), 7.61–7.57 (m, 3H), 7.45–7.36 (m, 3H), 7.31–7.28 (m, 1H), 7.11 (d, 2H, J=8.60 Hz), 7.05 (t, 1H, J=7.82 Hz), 6.82–6.75(m, 3H), 6.65–6.61 (m, 2H), 4.17 (t, 2H, J=6.65 Hz), 3.17 (d, 1H, J=13.69 Hz), 3.06 (d, 1H, J=13.69 Hz), 2.96 (t, 2H, J=6.65 Hz) 2.33 (s, 3H), 2.21 (s, 3H), 1.35 (s, 3H); HRMS (ES+) m/z exact mass calcd for C35H34NO5 548.2437, found 548.2415.

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-9d86b0c9b8644140844bd3491ae3f2fc
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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