1-(2,3-DICHLOROPHENYL)-2,5-DIHYDRO-1H-PYRROLE-2,5-DIONE synthesis

Yield:37010-53-0 37%

Reaction Conditions:

in diethyl ether at 20; for 2 h;

Steps:

11

General procedure: General Procedure A: Maleic anhydride was placed in a round-bottomed flask and to it was added anhydrous Et₂0 (2 mL/mmol) at RT. Upon complete dissolution of the maleic anhydride, the appropriate substituted aniline (1.1 mol equiv) dissolved in anhydrous Et₂0 (1 mL/mmol) was added dropwise at RT. The reaction was stirred for approximately 2 h resulting in the formation of a white precipitate. The reaction was then concentrated in vacuo, cooled in an ice bath and the N-substituted maleanic acid precipitate was isolated by filtration. The filter cake was then added to a round-bottomed flask charged with sodium acetate (1 mol equiv) and acetic anhydride (0.5 mL/mmol). The reaction was heated to 100 °C and stirred for 20-30 min after which it was cooled to room temperature and poured into ice water (50 mL). The organic products were extracted with EtOAc (3 x 15 mL), washed with water (3 x 15 mL) and brine (15 mL), dried with anhydrous Na₂S0₄, filtered and concentrated in vacuo. The resulting product was then purified using automated column chromatography. The title compound was synthesized from maleic anhydride (2.5 g, 26 mmol) and 2,3-dichloroaniline (4.5 g, 28 mmol) according to general procedure A and isolated as an off-white solid (2.3 g, 37%). 1H-NMR (400 MHz, CDCls): δ 7.58 (dd, J= 1.5 Hz, J= 6.7 Hz, 1H), 7.33 (t, J= 8.0 Hz, 1H), 7.21 (dd, J = 1.5 Hz, J = 6.4 Hz, 1H), 6.91 (s, 2H). ¹³C-NMR (100 MHz, CDC1₃): δ 168.4, 134.6, 134.3, 132.2, 131.5, 130.7, 129.0, 127.7. ESI-HRMS: calc. for Ci₀H₅Ci₂NO₂: [M+H]⁺ = m/z 241.9770, found: [M+H]⁺ = m/z 241.9776

References:

WO2014/85545,2014,A1 Location in patent:Page/Page column 43; 47