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

HRID 2238242Notes

Reaction equation

HRID 2238242 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 esterYield 86%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21864698Diethyl ether methanolSolvent

Conditions

Temperature
4 °C

Procedure

To a stirred suspension of 9 (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 (1.0 L) was removed from the reaction mixture and cooled overnight at 4° C. Solid separated was filtered and mother liquor was evaporated to dryness under reduced pressure. The residue obtained was re-dissolved in a mixture of MeOH-diethylether (1:1, 3.0 L). On standing overnight at 4° C., the solution yielded more solids. Solid from both the lots were combined and dried overnight in vacuum oven at 40° C. to give 10 as yellow solid (362.5 g, 86%): mp 106-108° C.; mp 225-226° C.; 1H NMR (360 MHz, DMSO-d6): δ 12.53 (br s, 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), 7.13 (overlapped d, J=8.3 Hz, 2H), 7.11 (overlapped d, J=8.6 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); MS (EI) m/z 518[M]+; Anal. (C28H23NO7S) C, H, N.

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 (1.0 L) was removed from the reaction mixture
  6. customSolid separated
  7. filtrationwas filtered
  8. custommother liquor was evaporated to dryness under reduced pressure
  9. customThe residue obtained
  10. customthe solution yielded more solids
  11. customdried overnight in vacuum oven at 40° C.

Sources & evidence

ORD record
ord-c1b5db5f68a74fd9a0dd5adc8ec6b501
Source dataset
uspto-grants-2010_05
Patent number
US07718682B2

Reaction notes

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