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

HRID 348324Notes

Reaction equation

HRID 348324 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](O)=[CH:9][CH:8]=1)C.[C:24]1(C2C=CC=CC=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:37]S(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:29]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH:24]=[CH:25][C:26]([C:30]2[O:31][C:32]([CH3:48])=[C:33]([CH2:35][CH2:36][O:37][C:10]3[CH:9]=[CH:8][C:7]([CH2:6][C:5]([O:15][C:16]4[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=4)([CH3:14])[C:4]([OH:3])=[O:23])=[CH:12][CH:11]=3)[N:34]=2)=[CH:27][CH:28]=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 693158912-(4-Chlorophenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester

Product 1

HCID 102813933-{4-[2-(2-Biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-phenyl}-2-(4-chloro-phenoxy)-2-methyl-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) (see Ex. 26, Part C), toluene-4-sulfonic acid 2-(2-biphenyl-3-yl-5-methyloxazol-4-yl)ethyl ester (0.030 mmol) (see Ex. 2, Part F) 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-chloro-phenoxy)-2-methyl-propionic acid. 1H NMR (400 MHz, CDCl3δ 8.12 (t, 1H, J=19.94 Hz), 7.87 (td, 1H, J=19.16 Hz, 7.43 Hz), 7.61 (t, 3H, J=7.43 Hz), 7.48–7.28 (m, 4H), 7.08 (t, 4H, J=6.65 Hz), 6.77 (td, 4H, J=24.63 Hz, 12.12 Hz), 4.16 (t, 2H, J=6.65 Hz), 3.18 (d, 1H, J=13.29 Hz), 3.00 (d, 1H, J=13.29 Hz), 2.90 (t, 2H, J=6.65 Hz), 2.52 (d, 1H, J=15.25 Hz), 2.32 (t, 2H, J=19.55 Hz), 1.29 (s, 3H) MS (ES+) m/z mass calcd for C34H31ClNO5 568.19, found 568.2.

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-e36a9357b173429ea0329063de9ca837
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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