4-Chloro-1,3-dioxolan-2-one

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

Procedure: A solution of 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (1.0 g), 4-chloro-1,3-dioxolan-2-one (0.41 g) and triethylamine in DMF was stirred at 90° C. for 12 hrs. The reaction mixture was concentrated, and the residue was dissolved in chloroform and 1N hydrochloric acid. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound (0.20 g, 22%) as a colorless solid. The reaction mixture was concentrated the residue was dissolved in chloroform The organic layer was separated dried over anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography

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

Procedure: A solution of 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (1.0 g), 4-chloro-1,3-dioxolan-2-one (0.41 g) and triethylamine in DMF was stirred at 90° C. for 12 hrs. The reaction mixture was concentrated, and the residue was dissolved in chloroform and 1N hydrochloric acid. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound (0.20 g, 22%) as a colorless solid. The reaction mixture was concentrated the residue was dissolved in chloroform The organic layer was separated dried over anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1,3-dioxolan-2-one (1.35 g, 11 mmol) was added at room temperature to a solution of potassium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (6.66 g, 10 mmol) and sodium iodide (0.15 g, 1 mmol) in dry DMF (50 ml). After stirring at 50° C. for 6 hours and at room temperature for 4 days the solvent was removed at reduced pressure. The residue was dissolved in chloroform (100 ml) and washed four times with a saturated sodium hydrogen carbonate solution and finally twice with water. After treatment with magnesium sulfate the solution was finally evaporated to dryness. Yield: 5.6 g. Purity by HPLC: 93%. 1H-NMR (DMSO-d6): delta=1.67 (N (CH3)COCH3); 2.05(NCOCH3); 2.96(NCH3); 4.7; 4.9(CH2); 7.02(CH); 10.14 ppm(NH). was removed at reduced pressure The residue was dissolved in chloroform (100 ml) washed four times with a saturated sodium hydrogen carbonate solution After treatment with magnesium sulfate the solution was finally evaporated to dryness

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1,3-dioxolan-2-one (1.35 g, 11 mmol) was added at room temperature to a solution of potassium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (6.66 g, 10 mmol) and sodium iodide (0.15 g, 1 mmol) in dry DMF (50 ml). After stirring at 50° C. for 6 hours and at room temperature for 4 days the solvent was removed at reduced pressure. The residue was dissolved in chloroform (100 ml) and washed four times with a saturated sodium hydrogen carbonate solution and finally twice with water. After treatment with magnesium sulfate the solution was finally evaporated to dryness. Yield: 5.6 g. Purity by HPLC: 93%. 1H-NMR (DMSO-d6): delta=1.67 (N (CH3)COCH3); 2.05(NCOCH3); 2.96(NCH3); 4.7; 4.9(CH2); 7.02(CH); 10.14 ppm(NH). was removed at reduced pressure The residue was dissolved in chloroform (100 ml) washed four times with a saturated sodium hydrogen carbonate solution After treatment with magnesium sulfate the solution was finally evaporated to dryness

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

Procedure: Monochloroethylene carbonate was prepared in the same manner as in (2) above. The prepared monochloroethylene carbonate (494 g) was dissolved in dibutyl carbonate (500 mL), and placed in a reaction vessel (2-liter volume). To the reaction vessel was dropwise added triethylamine (440 g) at 50° C. for 6 hours, for performing a reaction. The mixture was stirred further for 14 hours. The reaction mixture was cooled to room temperature, and triethylamine hydrochloride was filtered off and washed sufficiently with dibutyl carbonate. The filtrate (2,100 g) was placed at 30 mmHg to distill excessive triethylamine off, and then to collect 390 g of a vinylene carbonate distillate. The vinylene carbonate distillate was treated with silica gel and then subjected to fractional distillation at 30 mmHg to obtain 195 g of vinylene carbonate (b.p.: 73° C.) containing an extremely small amount of contaminant. The obtained vinylene carbonate was named “High purity vinylene carbonate”. placed in a reaction vessel at 50° C. for 6 hours a reaction triethylamine hydrochloride was filtered off washed sufficiently with dibutyl carbonate to distill excessive triethylamine off, and then to collect 390 g of a vinylene carbonate distillate The vinylene carbonate distillate was treated with silica gel subjected to fractional distillation at 30 mmHg

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

Procedure: A solution of 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (1.0 g), 4-chloro-1,3-dioxolan-2-one (0.41 g) and triethylamine in DMF was stirred at 90° C. for 12 hrs. The reaction mixture was concentrated, and the residue was dissolved in chloroform and 1N hydrochloric acid. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound (0.20 g, 22%) as a colorless solid. The reaction mixture was concentrated the residue was dissolved in chloroform The organic layer was separated dried over anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1,3-dioxolan-2-one (1.35 g, 11 mmol) was added at room temperature to a solution of potassium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (6.66 g, 10 mmol) and sodium iodide (0.15 g, 1 mmol) in dry DMF (50 ml). After stirring at 50° C. for 6 hours and at room temperature for 4 days the solvent was removed at reduced pressure. The residue was dissolved in chloroform (100 ml) and washed four times with a saturated sodium hydrogen carbonate solution and finally twice with water. After treatment with magnesium sulfate the solution was finally evaporated to dryness. Yield: 5.6 g. Purity by HPLC: 93%. 1H-NMR (DMSO-d6): delta=1.67 (N(CH3)COCH3); 2.05(NCOCH3); 2.96(NCH3); 4.7; 4.9(CH2); 7.02(CH); 10.14 ppm(NH). was removed at reduced pressure The residue was dissolved in chloroform (100 ml) washed four times with a saturated sodium hydrogen carbonate solution After treatment with magnesium sulfate the solution was finally evaporated to dryness

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1,3-dioxolan-2-one (1.35 g, 11 mmol) was added at room temperature to a solution of potassium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (6.66 g, 10 mmol) and sodium iodide (0.15 g, 1 mmol) in dry DMF (50 ml). After stirring at 50° C. for 6 hours and at room temperature for 4 days the solvent was removed at reduced pressure. The residue was dissolved in chloroform (100 ml) and washed four times with a saturated sodium hydrogen carbonate solution and finally twice with water. After treatment with magnesium sulfate the solution was finally evaporated to dryness. Yield: 5.6 g. Purity by HPLC: 93%. 1H-NMR (DMSO-d6): delta=1.67 (N(CH3)COCH3); 2.05(NCOCH3); 2.96(NCH3); 4.7; 4.9(CH2); 7.02(CH); 10.14 ppm(NH). was removed at reduced pressure The residue was dissolved in chloroform (100 ml) washed four times with a saturated sodium hydrogen carbonate solution After treatment with magnesium sulfate the solution was finally evaporated to dryness

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

Procedure: A solution of 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (1.0 g), 4-chloro-1,3-dioxolan-2-one (0.41 g) and triethylamine in DMF was stirred at 90° C. for 12 hrs. The reaction mixture was concentrated, and the residue was dissolved in chloroform and iN hydrochloric acid. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound (0.20 g, 22%) as a colorless solid. The reaction mixture was concentrated the residue was dissolved in chloroform and iN hydrochloric acid The organic layer was separated dried over anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1,3-dioxolan-2-one (1.35 g, 11 mmol) was added at room temperature to a solution of potassium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (6.66 g, 10 retool) and sodium iodide (0.15 g, 1 retool) in dry DMF (50 ml). After stirring at 50° C. for 6 hours and at room temperature for 4 days the solvent was removed at reduced pressure. The residue was dissolved in chloroform (100 ml) and washed four times with a saturated sodium hydrogen carbonate solution and finally twice with water. After treatment with magnesium sulfate the solution was finally evaporated to dryness. Yield: 5.6 g. Purity by HPLC: 93%. 1H-NMR (DMSO-d6): delta=1.67 (N(CH3)COCH3); 2.05(NCOCH3); 2.96 (NCH3); 4.7; 4.9(CH2); 7.02(CH); 10.14 ppm (NH). was removed at reduced pressure The residue was dissolved in chloroform (100 ml) washed four times with a saturated sodium hydrogen carbonate solution After treatment with magnesium sulfate the solution was finally evaporated to dryness

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

Procedure: A solution of 2-ethoxy-1-{[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-carboxylic acid (1.0 g), 4-chloro-1,3-dioxolan-2-one (0.41 g) and triethylamine in DMF was stirred at 90° C. for 12 hrs. The reaction mixture was concentrated, and the residue was dissolved in chloroform and 1N hydrochloric acid. The organic layer was separated, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography to give the title compound (0.20 g, 22%) as a colorless solid. The reaction mixture was concentrated the residue was dissolved in chloroform The organic layer was separated dried over anhydrous sodium sulfate concentrated The residue was purified by silica gel column chromatography

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloro-1,3-dioxolan-2-one (1.35 g, 11 mmol) was added at room temperature to a solution of potassium 5-(N-acetylamino)-3-(N-acetyl-N-methylamino)-2,4,6-triiodobenzenecarboxylate (6.66 g, 10 mmol) and sodium iodide (0.15 g, 1 mmol) in dry DMF (50 ml). After stirring at 50° C. for 6 hours and at room temperature for 4 days the solvent was removed at reduced pressure. The residue was dissolved in chloroform (100 ml) and washed four times with a saturated sodium hydrogen carbonate solution and finally twice with water. After treatment with magnesium sulfate the solution was finally evaporated to dryness. Yield: 5.6 g. Purity by HPLC: 93%. 1H-NMR (DMSO-d6): delta=1.67 (N (CH3)COCH3); 2.05(NCOCH3); 2.96(NCH3); 4.7; 4.9(CH2); 7.02(CH); 10.14 ppm(NH). was removed at reduced pressure The residue was dissolved in chloroform (100 ml) washed four times with a saturated sodium hydrogen carbonate solution After treatment with magnesium sulfate the solution was finally evaporated to dryness