Potassium Carbonate → 2-(4-{2-[5-Methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-hexanoic acid

HRID 348377Notes

Reaction equation

HRID 348377 reaction equation
C([O:3][C:4](=[O:25])[C:5]([CH2:17][C:18]1[CH:23]=[CH:22][C:21](O)=[CH:20][CH:19]=1)([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:6][CH2:7][CH2:8][CH3:9])C.[CH3:26][C:27]1[O:31][C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)[CH:33]=2)=[N:29][C:28]=1[CH2:43][CH2:44][O:45]S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[CH3:26][C:27]1[O:31][C:30]([C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([C:38]3[S:39][CH:40]=[CH:41][CH:42]=3)[CH:33]=2)=[N:29][C:28]=1[CH2:43][CH2:44][O:45][C:21]1[CH:22]=[CH:23][C:18]([CH2:17][C:5]([O:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)([CH2:6][CH2:7][CH2:8][CH3:9])[C:4]([OH:25])=[O:3])=[CH:19][CH:20]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693198712-(4-Hydroxybenzyl)-2-phenoxyhexanoic acid ethyl esterHCID 86593517Toluene-4-sulfonic acid 2-[5-methyl-2-(3-thiophen-2-ylphenyl)oxazol-4-yl]ethyl ester

Product 1

HCID 101210182-(4-{2-[5-Methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-hexanoic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(4-hydroxybenzyl)-2-phenoxyhexanoic acid ethyl ester (0.030 mmol) (see Ex 61, Part C), toluene-4-sulfonic acid 2-[5-methyl-2-(3-thiophen-2-ylphenyl)oxazol-4-yl]ethyl ester (0.030 mmol) (see Ex. 5, 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-(4-{2-[5-methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-benzyl)-2-phenoxy-hexanoic acid. 1H NMR (400 MHz, CDCl3) δ 8.15–8.12 (m, 1H), 7.79 (d, 1H, J=7.43 Hz), 7.57 (d, 1H, J=7.82 Hz), 7.37–7.32 (m, 2H), 7.24–7.18 (m, 3H), 7.01 (dd, 1H, J=5.08 Hz, J=3.52 Hz), 6.99–6.87 (m, 5H), 6.68 (d, 2H, J=8.99 Hz), 4.10 (t, 2H, J=6.65 Hz), 3.21 (s, 2H), 2.91 (t, 2H, J=6.65 Hz), 2.31 (s, 3H), 2.02–1.88 (m, 2H), 1.34–1.08 (m, 4H), 0.71 (t, 3H, J=7.04 Hz); MS (ES+) calcd for C35H36NO5S: Found m/e 582.2 (M+1, 100%).

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-537c16e2769d45bc9f83d86d45747dbe
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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