Potassium Carbonate → 2-{4-[2-(2-Biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-benzyl}-2-phenoxy-hexanoic acid

HRID 348375Notes

Reaction equation

HRID 348375 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][C:35]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)=[CH:34][CH:33]=2)=[N:29][C:28]=1[CH2:44][CH2:45][O:46]S(C1C=CC(C)=CC=1)(=O)=O.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[C:35]1([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:36]=[CH:37][C:32]([C:30]2[O:31][C:27]([CH3:26])=[C:28]([CH2:44][CH2:45][O:46][C:21]3[CH:22]=[CH:23][C:18]([CH2:17][C:5]([O:10][C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)([CH2:6][CH2:7][CH2:8][CH3:9])[C:4]([OH:25])=[O:3])=[CH:19][CH:20]=3)[N:29]=2)=[CH:33][CH:34]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 12966835Toluene-4-sulfonic acid 2-(2-biphenyl-4-yl-methyl-oxazol-4-yl)ethyl esterHCID 693198712-(4-Hydroxybenzyl)-2-phenoxyhexanoic acid ethyl ester

Product 1

HCID 101669662-{4-[2-(2-Biphenyl-4-yl-5-methyl-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), toluene-4-sulfonic acid 2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethyl ester (0.030 mmol) (see Ex. 1, Part I) 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-(2-biphenyl-4-yl-5-methyl-oxazol-4-yl)-ethoxy]-benzyl}-2-phenoxy-hexanoic acid. 1H NMR (400 MHz, CDCl3) δ 8.02 (d, 2H, J=8.60 Hz), 7.65–7.61 (m, 4H), 7.46 (t, 2H, J=7.62 Hz), 7.38–7.26 (m, 3H), 7.07–6.96 (m, 5H), 6.76 (d, 2H, J=8.60 Hz), 4.18 (t, 2H, J=6.65 Hz), 3.29 (s, 2H), 2.97 (t, 2H, J=6.65 Hz), 2.38 (s, 3H), 2.08–1.98 (m, 2H), 1.42–1.18 (m, 4H), 0.79 (t, 3H, J=7.04 Hz); MS (ES+) calcd for C37H38NO5: Found m/e 576.3 (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-5bf93ee37f9c427f82d794dbe519eb94
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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