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

HRID 348318Notes

Reaction equation

HRID 348318 reaction equation
C([O:3][C:4](=[O:23])[C:5]([O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[F:22])([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1)C.[CH3:24][C:25]1[O:29][C:28]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[S:37][CH:38]=[CH:39][CH:40]=3)=[CH:32][CH:31]=2)=[N:27][C:26]=1[CH2:41][CH2:42]OS(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[F:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[O:15][C:5]([CH3:14])([CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:42][CH2:41][C:26]2[N:27]=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([C:36]4[S:37][CH:38]=[CH:39][CH:40]=4)=[CH:32][CH:31]=3)[O:29][C:25]=2[CH3:24])=[CH:11][CH:12]=1)[C:4]([OH:3])=[O:23]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 577192632-(2-Fluorophenoxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl esterHCID 86593515Toluene-4-sulfonic acid 2-(5-methyl-2-(4-thiophen-2-yl-phenyl)-oxazol-4-yl)ethyl ester

Product 1

HCID 101877492-(2-Fluoro-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-(2-fluoro-phenoxy)-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-(2-fluoro-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 7.96 (d, 2H, J=8.60 Hz), 7.38 (d, 2H, J=3.52 Hz), 7.33 (d, 2H, J=3.52 Hz), 7.23 (d, 2H, J=8.60 Hz), 7.10 (dd, 2H, J=5.08 Hz, 3.52 Hz), 7.08–7.04 (m, 1H), 7.00–6.96 (m, 2H), 6.82 (d, 2H, J=8.60 Hz), 4.19 (t, 2H, J=6.65 Hz), 3.26 (d, 1H, J=14.08 Hz), 3.20 (d, 1H, J=14.08 Hz), 3.01 (t, 2H, J=6.65 Hz), 2.38 (s, 3H), 1.43 (s, 3H). MS (ES+) m/z mass calcd for C32H28FNO5S 558.17, number found 558.2.

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-4aeb4c22ca234bebb608d5e1f6c2c3c9
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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