Ammonium formate → Methyl 3-(3,5-dimethoxyphenyl)-2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]prop-2-enoate

HRID 2217607Notes

Reaction equation

HRID 2217607 reaction equation
[CH3:1][O:2][C:3](=[O:37])[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:30]3[S:34][C:33](=[O:35])[NH:32][C:31]3=[O:36])=[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.C([O-])=O.[NH4+]>[Pt].C(O)(=O)C>[CH3:1][O:2][C:3](=[O:37])[C:4]([C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH:30]3[S:34][C:33](=[O:35])[NH:32][C:31]3=[O:36])=[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

Participants

5

Reactant 2

HCID 2723923Ammonium formateHCID 731978483-(3,5-Dimethoxyphenyl)-2-{4-[4-(2,4-dioxothiazolidin-5-ylidenemethyl)-phenoxy]-phenyl}-acrylic acid methyl ester

Product 1

HCID 73197849Methyl 3-(3,5-dimethoxyphenyl)-2-[4-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]phenyl]prop-2-enoateYield 64.1%

Reagents, catalysts & solvents 2

HCID 23939PlatinumCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
124 °C

Procedure

Compound 10 (20 g, 38.6 mmol), ammonium formate (150 g, 2.38 mol), 10% Pt/C (dry, 4 g) and acetic acid (660 mL) were combined into a round bottom flask equipped with reflux condenser, thermometer and mechanical stirrer. The reactor was evacuated and purged three times with nitrogen then, heated to a steady reflux (ca. 124° C.). Reaction was completed within 15 h and allowed to cool with stirring to ambient room temperature. After cooling, the mixture was filtered though a pad of Celite® (5 g) and the filter pad washed with fresh acetic acid (2×100 mL). The mother liquor and washes were combined and concentrated. The residue was then diluted with dichloromethane (400 mL), and the combined organics were extracted twice with water (400 mL) and 5% bicarbonate (400 mL). The organic portion was then dried and poured through silica gel (30 g) and washed with dichloromethane (2×100 mL). The washes were combined and concentrated. The residue was diluted with ethanol, allowed to cool to 60° C. and seed crystals were added. This slurry was stirred at 50° C. for about 30 min then allowed to cool to ambient room temperature to yield compound 11 (12.85 g, 64%) with an HPLC assay of 98.1%.

Workup

  1. customequipped
  2. temperaturewith reflux condenser
  3. customThe reactor was evacuated
  4. custompurged three times with nitrogen
  5. temperatureheated to
  6. customReaction
  7. temperatureto cool
  8. temperatureAfter cooling
  9. filtrationthe mixture was filtered though a pad of Celite® (5 g)
  10. washthe filter pad washed with fresh acetic acid (2×100 mL)
  11. concentrationconcentrated
  12. additionThe residue was then diluted with dichloromethane (400 mL)
  13. extractionthe combined organics were extracted twice with water (400 mL) and 5% bicarbonate (400 mL)
  14. customThe organic portion was then dried
  15. additionpoured through silica gel (30 g)
  16. washwashed with dichloromethane (2×100 mL)
  17. concentrationconcentrated
  18. additionThe residue was diluted with ethanol
  19. temperatureto cool to 60° C.
  20. additionseed crystals were added
  21. stirringThis slurry was stirred at 50° C. for about 30 min
  22. temperatureto cool to ambient room temperature

Sources & evidence

ORD record
ord-643b9d99d4cd4f418f8c8cb5e8faa487
Source dataset
uspto-grants-2008_08
Patent number
US07407978B2

Reaction notes

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