Reaction #685009

Reaction equation

(2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone

phthalic anhydride

→

2-[3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl]isoindoline-1,3-dione

Solvents

acetic acid

Conditions

Workup

1. 1
   Otherprepared
2. 2
   Temperaturethe mixture is heated
3. 3
   Temperatureto reflux for 15 h
4. 4
   OtherThe solvent is evaporated in vacuo
5. 5
   workup.DISSOLUTIONthe residual material is dissolved in ethyl acetate (20 mL)
6. 6
   WashThe organic solution is washed with a saturated aqueous solution of NaHCO3 (5 mL), water (5 mL)
7. 7
   Dryingbrine (5 mL), dried (Na2SO4)
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo
10. 10
    Filtrationfiltered

Procedure

To a solution of (2-amino-4,5-dimethylthiophen-3-yl)(4-chlorophenyl)methanone (532 mg, 2 mmol; prepared as described in U.S. Pat. No. 6,323,214) in acetic acid (15 mL) is added phthalic anhydride (360 mg, 2.4 mmol) and the mixture is heated to reflux for 15 h. The solvent is evaporated in vacuo and the residual material is dissolved in ethyl acetate (20 mL). The organic solution is washed with a saturated aqueous solution of NaHCO3 (5 mL), water (5 mL), then brine (5 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The crude product is stirred for 1 h in petroleum ether (20 mL), then filtered, affording (2-[3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl]isoindoline-1,3-dione as a yellow powder. 1H NMR (CDCl3) δ: 2.10 (s, 3H), 2.43 (s, 3H), 7.24 (d, J=8.4 Hz, 2H), 7.64 (d, J=8.4 Hz, 2H), 7.78 (m, 4H).

Source