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

HRID 1270691Notes

Reaction equation

HRID 1270691 reaction equation
[CH3:1][O:2][C:3](=[O:31])[C: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)=[CH: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.CO.C(OCC)C>[CH3:1][O:2][C:3](=[O:31])[C: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)=[CH:5][C:6]1[CH:7]=[C:8]([O:14][CH3:15])[CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1

Participants

7

Reactant 4

HCID 243Benzoic AcidHCID 5437ThiazolidinedioneHCID 8082PiperidineHCID 731978473-(3,5-Dimethoxyphenyl)-2-[4-(4-formylphenoxy)-phenyl]-acrylic acid methyl ester

Product 1

HCID 731978483-(3,5-Dimethoxyphenyl)-2-{4-[4-(2,4-dioxothiazolidin-5-ylidenemethyl)-phenoxy]-phenyl}-acrylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21864698Diethyl ether methanolSolvent

Procedure

To a stirred suspension of Compound VI (352 g, 0.82 mol) in anhydrous toluene (2.5 L), 2,4-thiazolidinedione (98.6 g, 0.84 mol), benzoic acid (134 g, 1.10 mol) and piperidine (107.4 g, 1.26 mol) was added sequentially and heated at reflux temperature with continuous removal of water with the help of Dean-Stark apparatus for 5 h. Toluene (1 L) was removed from the reaction mixture and the mixture was placed overnight in a 4° C. cold room. Solid separated was filtered off and mother liquor was evaporated to dryness under reduced pressure. The residue obtained was redissolved in a mixture of MeOH-diethylether (1:1, 3 L). Solution on standing overnight at 4° C. yielded more solids. The solid was filtered; both the crops were pooled together and dried overnight in vacuum oven at 40° C. Yield: 362.5 g (86%). 1H NMR (DMSO-d6): δ 12.53 (br, 1H), 7.78 (s, 1H), 7.73 (s, 1H), 7.63 (d, J=9.2 Hz, 2H), 7.25 (d, J=9.2 Hz, 2H), 7.15 (d, J=4.3 Hz, 2H), 7.12 (d, J=4.3 Hz, 2H), 6.42 (t, J=2.2 Hz, 1H), 6.27 (d, J=2.2 Hz, 2H ), 3.73 (s, 3H), and 3.59 (s, 6H).

Workup

  1. additionwas added sequentially
  2. temperatureheated
  3. temperatureat reflux temperature
  4. customwith continuous removal of water with the help of Dean-Stark apparatus for 5 h
  5. customToluene (1 L) was removed from the reaction mixture
  6. customSolid separated
  7. filtrationwas filtered off
  8. custommother liquor was evaporated to dryness under reduced pressure
  9. customThe residue obtained
  10. waitSolution on standing overnight at 4° C.
  11. customyielded more solids
  12. filtrationThe solid was filtered
  13. customdried overnight in vacuum oven at 40° C

Sources & evidence

ORD record
ord-38f82818262e48c4abfbe6c4b57fee6a
Source dataset
uspto-grants-2007_04
Patent number
US07202366B2

Reaction notes

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