Benzoic Acid → 3-(3,5-Dimethoxyphenyl)-2-{4-[4-(2,4-dioxothiazolidin-5-ylidenemethyl)-phenoxy]-phenyl}-propionic acid methyl ester

HRID 2217613Notes

Reaction equation

HRID 2217613 reaction equation
[CH3:1][O:2][C:3](=[O:31])[CH:4]([C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]=O)=[CH:25][CH:24]=2)=[CH:18][CH:17]=1)[CH2:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[CH:7]=1.[S:32]1[CH2:36][C:35](=[O:37])[NH:34][C:33]1=[O:38].C(O)(=O)C1C=CC=CC=1.N1CCCCC1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:31])[CH:4]([C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH:29]=[C:36]3[S:32][C:33](=[O:38])[NH:34][C:35]3=[O:37])=[CH:25][CH:24]=2)=[CH:18][CH:17]=1)[CH2:5][C:6]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[CH:7]=1

Participants

6

Reactant 4

HCID 243Benzoic AcidHCID 5437ThiazolidinedioneHCID 8082PiperidineHCID 210512573-(3,5-Dimethoxyphenyl)-2-[4-(4-formylphenoxy)-phenyl]-propionic acid methyl ester

Product 1

HCID 865896813-(3,5-Dimethoxyphenyl)-2-{4-[4-(2,4-dioxothiazolidin-5-ylidenemethyl)-phenoxy]-phenyl}-propionic acid methyl esterYield 81.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred suspension of 16 (1.81 g, 4.3 mmol) in anhydrous toluene (25 mL), 2,4-thiazolidinedione (0.56 g, 4.74 mmol), benzoic acid (0.68 g, 5.60 mmol) and piperidine (0.60 mL, 6.03 mmol) was added sequentially and heated at reflux temperature with continuous removal of water using a Dean-Stark apparatus for 2 h. Solvent was evaporated to dryness under reduced pressure. The residue obtained was purified by silica gel chromatography, eluted with hexane-ethyl acetate (1:1) to yield 17 (1.82 g, 81%): mp 104-106° C.; 1H NMR (400 MHz, DMSO-d6) δ 12.53 (br s, 1H), 7.76 (s, 1H), 7.60 (d, J=8.7 Hz, 2H), 7.35 (d, J=8.7 Hz, 2H), 7.07 (d, J=4.8 Hz, 2H), 7.03 (d, J=4.8 Hz, 2H), 6.33-6.28 (m, 3H), 4.01 (t, J=7.5 Hz, 1 Hz), 3.66 (s, 6H), 3.56 (s, 3H), 3.22 (dd, J=13.8 and 8.4 Hz, 1H), 2.90 (dd, J=13.5 and 7.2 Hz, 1H); MS (EI) m/z 520[M]+; Anal. (C28H25NO7S) C: calculated, 64.73; found, 65.89; H: calculated, 4.85; found, 5.08, N: calculated, 2.70; found, 2.56.

Workup

  1. additionwas added sequentially
  2. temperatureheated
  3. temperatureat reflux temperature
  4. customwith continuous removal of water using a Dean-Stark apparatus for 2 h
  5. customSolvent was evaporated to dryness under reduced pressure
  6. customThe residue obtained
  7. customwas purified by silica gel chromatography
  8. washeluted with hexane-ethyl acetate (1:1)

Sources & evidence

ORD record
ord-ede6c21c87164f7faa5897e8af28283a
Source dataset
uspto-grants-2008_08
Patent number
US07407978B2

Reaction notes

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