Potassium Carbonate → 2-(Benzo[1,3]dioxol-5-yloxy)-2-methyl-3-(4-{2-[5-methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy)-phenyl)-propionic acid

HRID 348371Notes

Reaction equation

HRID 348371 reaction equation
C([O:3][C:4](=[O:25])[C:5]([O:15][C:16]1[CH:24]=[CH:23][C:19]2[O:20][CH2:21][O:22][C:18]=2[CH:17]=1)([CH3:14])[CH2:6][C:7]1[CH:12]=[CH:11][C:10](O)=[CH:9][CH:8]=1)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>[O:20]1[C:19]2[CH:23]=[CH:24][C:16]([O:15][C:5]([CH3:14])([CH2:6][C:7]3[CH:12]=[CH:11][C:10]([O:45][CH2:44][CH2:43][C:28]4[N:29]=[C:30]([C:32]5[CH:37]=[CH:36][CH:35]=[C:34]([C:38]6[S:39][CH:40]=[CH:41][CH:42]=6)[CH:33]=5)[O:31][C:27]=4[CH3:26])=[CH:9][CH:8]=3)[C:4]([OH:25])=[O:3])=[CH:17][C:18]=2[O:22][CH2:21]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 693164102-(Benzo[1,3]dioxol-5-yloxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl esterHCID 86593517Toluene-4-sulfonic acid 2-[5-methyl-2-(3-thiophen-2-ylphenyl)oxazol-4-yl]ethyl ester

Product 1

HCID 103037572-(Benzo[1,3]dioxol-5-yloxy)-2-methyl-3-(4-{2-[5-methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy)-phenyl)-propionic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

A mixture of 2-(benzo[1,3]dioxol-5-yloxy)-3-(4-hydroxyphenyl)-2-methyl-propionic acid ethyl ester (0.030 mmol) (see Ex. 58, 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-(benzo[1,3]dioxol-5-yloxy)-2-methyl-3-(4-{2-[5-methyl-2-(3-thiophen-2-yl-phenyl)-oxazol-4-yl]-ethoxy}-phenyl)-propionic acid. 1H NMR (400 MHz, CDCl3) δ 8.19 (t, 1H, J=1.71 Hz), 7.85–7.82 (m, 1H), 7.67–7.63 (m, 1H), 7.42 (t, 1H, J=7.82 Hz), 7.38–7.37 (m, 1H), 7.28–7.26 (m, 1H), 7.13 (d, 2H, J=8.79 Hz), 7.06 (dd, 1H, J=4.88 Hz, J=3.42 Hz), 6.79 (d, 2H, J=8.79 Hz), 6.60 (d, 1H, J=8.30 Hz), 6.40 (d, 1H, J=2.44 Hz), 6.32 (dd, 1H, J=8.30 Hz, J=2.44 Hz), 5.87 (d, 2H, J=0.98 Hz), 4.19 (t, 2H, J=6.11 Hz), 3.15 (d, 1H, J=14.17 Hz), 3.04–3.01 (m, 3H), 2.39 (s, 3H), 1.30 (s, 3H);HRMS (ES+) m/z exact mass calcd for C33H30NO7S 584.1743, found 584.1744.

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-15e3225a09664b22b502c7c175b215c4
Source dataset
uspto-grants-2007_02
Patent number
US07176224B2

Reaction notes

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