2-(4,5-dimethyl-1-oxidopyridin-1-ium-2-yl)isoindole-1,3-dione

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(1,3-dioxoisoindolin-2-yl)-4,5-dimethylpyridine 1-oxide (1.5 g, 0.01 mol) in POCl3 (50 mL) was added Et3N (680 mg, 0.01 mol) at room temperature. The mixture was stirred at 80□ for 2 hr, and then carefully poured into the mixture of saturation NaHCO3 solution and ice water. The mixture was extracted with EtOAc (50 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give a crude residue that was purified by column chromatography on silica gel (10-15% ethyl acetate in petroleum ether) to give 2-(6-chloro-4,5-dimethylpyridin-2-yl)isoindoline-1,3-dione (650 mg, 41%). 1H NMR (300 MHz, CDCl3) δ 7.97-7.92 (m, 2H), 7.82-7.78 (m, 2H), 7.16 (s, 1H), 2.41 (s, 3H), 2.39 (s, 3H). The mixture was extracted with EtOAc (50 mL×3) The combined organic layers were dried over anhydrous Na2SO4 filtered evaporated under vacuum to give a crude residue that was purified by column chromatography on silica gel (10-15% ethyl acetate in petroleum ether)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4,5-dimethylpyridin-2-yl)-isoindoline-1,3-dione (1.7 g, 0.01 mol) in CH2Cl2 (50 mL) was added m-CPBA (3.5 g, 0.02 mol) at the room temperature. The mixture was stirred overnight, then quenched by addition of a saturated solution of Na2S2O3 (100 mL). The organic layer was separated and the aqueous phase was extracted with CH2Cl2 (50 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give 2-(1,3-dioxoisoindolin-2-yl)-4,5-dimethylpyridine 1-oxide (1.5 g, 83%), which was used directly in the next step. quenched by addition of a saturated solution of Na2S2O3 (100 mL) The organic layer was separated the aqueous phase was extracted with CH2Cl2 (50 mL×3) The combined organic layers were dried over anhydrous Na2SO4 filtered evaporated under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(1,3-dioxoisoindolin-2-yl)-4,5-dimethylpyridine 1-oxide (1.5 g, 0.01 mol) in POCl3 (50 mL) was added Et3N (680 mg, 0.01 mol) at room temperature. The mixture was stirred at 80□ for 2 hr, and then carefully poured into the mixture of saturation NaHCO3 solution and ice water. The mixture was extracted with EtOAc (50 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give a crude residue that was purified by column chromatography on silica gel (10-15% ethyl acetate in petroleum ether) to give 2-(6-chloro-4,5-dimethylpyridin-2-yl)isoindoline-1,3-dione (650 mg, 41%). 1H NMR (300 MHz, CDCl3) δ 7.97-7.92 (m, 2H), 7.82-7.78 (m, 2H), 7.16 (s, 1H), 2.41 (s, 3H), 2.39 (s, 3H). The mixture was extracted with EtOAc (50 mL×3) The combined organic layers were dried over anhydrous Na2SO4 filtered evaporated under vacuum to give a crude residue that was purified by column chromatography on silica gel (10-15% ethyl acetate in petroleum ether)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(4,5-dimethylpyridin-2-yl)-isoindoline-1,3-dione (1.7 g, 0.01 mol) in CH2Cl2 (50 mL) was added m-CPBA (3.5 g, 0.02 mol) at the room temperature. The mixture was stirred overnight, then quenched by addition of a saturated solution of Na2S2O3 (100 mL). The organic layer was separated and the aqueous phase was extracted with CH2Cl2 (50 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give 2-(1,3-dioxoisoindolin-2-yl)-4,5-dimethylpyridine 1-oxide (1.5 g, 83%), which was used directly in the next step. quenched by addition of a saturated solution of Na2S2O3 (100 mL) The organic layer was separated the aqueous phase was extracted with CH2Cl2 (50 mL×3) The combined organic layers were dried over anhydrous Na2SO4 filtered evaporated under vacuum