Phthalic Anhydride → 2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-(3-methoxyphenyl)-thiophene-3-carboxylic acid ethyl ester

HRID 2212288Notes

Reaction equation

HRID 2212288 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)=[CH:9][S:8][C:7]=1[NH2:19])=[O:5])[CH3:2].[C:20]1(=O)[O:25][C:23](=[O:24])[C:22]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:21]12>C(O)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)=[CH:9][S:8][C:7]=1[N:19]1[C:23](=[O:24])[C:22]2[C:21](=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:20]1=[O:25])=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 6811Phthalic AnhydrideHCID 690667Ethyl 2-amino-4-(3-methoxyphenyl)thiophene-3-carboxylate

Product 1

HCID 670738502-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-(3-methoxyphenyl)-thiophene-3-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 2-amino-4-(3-methoxyphenyl)thiophene-3-carboxylic acid ethyl ester (2 mmol, Example 18 & 19, Part B) and phthalic anhydride (2.2 mmol) in glacial acetic acid (20 mL) is heated at reflux overnight. After cooling to room temperature, the acetic acid is removed in vacuo and the residue triturated with petroleum ether. The crude product is collected by filtration, suspended in acetyl chloride (5 mL), and heated to reflux for one hour. After removing the solvent in vacuo, the residue is dissolved in ethyl acetate (30 mL), washed sequentially with 5% aqueous NaHCO3 (10 mL), water (10 mL), brine (10 mL), dried (Na2SO4), filtered, and concentrated in vacuo. Recrystallization affords the desired product.

Workup

  1. temperatureis heated
  2. temperatureat reflux overnight
  3. customthe acetic acid is removed in vacuo
  4. customthe residue triturated with petroleum ether
  5. filtrationThe crude product is collected by filtration
  6. temperatureheated
  7. temperatureto reflux for one hour
  8. customAfter removing the solvent in vacuo
  9. dissolutionthe residue is dissolved in ethyl acetate (30 mL)
  10. washwashed sequentially with 5% aqueous NaHCO3 (10 mL), water (10 mL), brine (10 mL)
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customRecrystallization

Sources & evidence

ORD record
ord-6461a1704ff54cfab95c24aafdef743b
Source dataset
uspto-grants-2006_09
Patent number
US07101905B2

Reaction notes

Loading…