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

HRID 2217610Notes

Reaction equation

HRID 2217610 reaction equation
[S:1]1[CH2:5][C:4](=[O:6])[NH:3][C:2]1=[O:7].C([Li])CCC.[CH3:13][O:14][C:15](=[O:43])[C:16]([C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]2[CH:40]=[CH:39][C:38]([CH2:41]Br)=[CH:37][CH:36]=2)=[CH:30][CH:29]=1)=[CH:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[CH:19]=1>C1COCC1>[CH3:13][O:14][C:15](=[O:43])[C:16]([C:28]1[CH:33]=[CH:32][C:31]([O:34][C:35]2[CH:40]=[CH:39][C:38]([CH2:41][CH:5]3[S:1][C:2](=[O:7])[NH:3][C:4]3=[O:6])=[CH:37][CH:36]=2)=[CH:30][CH:29]=1)=[CH:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[CH:21]=[C:20]([O:26][CH3:27])[CH:19]=1

Participants

5

Reactant 3

HCID 5437ThiazolidinedioneHCID 687897972-[4-(4-Bromomethylphenoxy)-phenyl]-3-(3,5-dimethoxyphenyl)-acrylic acid methyl esterHCID 178418339Butyllithium

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

2,4-Thiazolidinedione (2.83 g, 24.2 mmol) was dissolved in dry THF (170 mL) and cooled to 0° C. under argon. Butyllithium (1.6 M in hexanes, 30 mL, 48.0 mmol) was added dropwise. Stirring continued for 0.5 h at 0° C. Under argon, 13 (5.7 g, 11.8 mmol) was dissolved in dry THF (30 mL) and was added rapidly via syringe to the above suspension with rapid stirring. The temperature was maintained at 0° C. for 45 min before quenching with aqueous HCl (5%, 40 mL). Additional H2O (40 mL) was added and extracted with ethyl acetate (3×30 mL). Organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, filtered and the solvent was evaporated. Flash chromatography over silica gel using hexanes-ethyl acetate (3:2) as eluting solvent yielded the title compound, 11, (0.93 g, 15%). The melting point and 1H NMR of compound 11 made by this method were identical to those for compound 11 produced by the synthetic route starting from compound 10 described above.

Workup

  1. additionwas added rapidly via syringe to the above suspension with rapid stirring
  2. temperatureThe temperature was maintained at 0° C. for 45 min
  3. custombefore quenching with aqueous HCl (5%, 40 mL)
  4. additionAdditional H2O (40 mL) was added
  5. extractionextracted with ethyl acetate (3×30 mL)
  6. washwashed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. filtrationfiltered
  9. customthe solvent was evaporated
  10. washas eluting solvent

Sources & evidence

ORD record
ord-180c431bd2e64104a82fab3341c26a80
Source dataset
uspto-grants-2008_08
Patent number
US07407978B2

Reaction notes

Loading…