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

HRID 348376Notes

Reaction equation

HRID 348376 reaction equation
C([O:3][C:4](=[O:25])[C:5]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([OH:24])=[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.[C:26]1([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:31]=[CH:30][CH:29]=[C:28]([C:32]2[O:33][C:34]([CH3:50])=[C:35]([CH2:37][CH2:38]OS(C3C=CC(C)=CC=3)(=O)=O)[N:36]=2)[CH:27]=1.C([O-])([O-])=O.[K+].[K+].[OH-].[Na+]>C(O)C>[C:26]1([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)[CH:31]=[CH:30][CH:29]=[C:28]([C:32]2[O:33][C:34]([CH3:50])=[C:35]([CH2:37][CH2:38][O:24][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:3])=[O:25])=[CH:19][CH:20]=3)[N:36]=2)[CH:27]=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 693198712-(4-Hydroxybenzyl)-2-phenoxyhexanoic acid ethyl ester

Product 1

HCID 101447442-{4-[2-(2-Biphenyl-3-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) (see Ex 61, 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 2-{4-[2-(2-biphenyl-3-yl-5-methyl-oxazol-4-yl)-ethoxy]-benzyl}-2-phenoxy-hexanoic acid. 1H NMR (400 MHz, CDCl3) δ 8.12 (t, 1H, J=1.56 Hz), 7.86 (d, 1H, J=7.82 Hz), 7.58–7.54 (m, 3H), 7.42–7.35 (m, 3H), 7.30–7.18 (m, 3H), 6.97 (t, 1H, J=7.23 Hz), 6.93–6.87 (m, 4H), 6.68 (d, 2H, J=8.60 Hz), 4.11 (t, 2H, J=6.65 Hz), 3.21 (s, 2H), 2.89 (t, 2H, J=6.65 Hz), 2.29 (s, 3H), 2.02–1.89 (m, 2H), 1.33–1.09 (m, 4H), 0.71 (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-48b8085ed9c4487cbad845e67d649d5d
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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