N-Methylsaccharin

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 590 mg. (3 mmole) of N-methylsaccharin and 1.02 g. (6 mmole) of N-(2-pyridyl)chloroacetamide in 3 ml. of dimethylformamide at 40° C. was added 250 mg. (10.3 mmole) of 99% sodium hydride portionwise over a period of one hour. The reaction mixture was allowed to stir at 40° C. for 2.5 hours and was then added to 100 ml. of 5% hydrochloric acid solution and 300 ml. of ice. The precipitate was filtered and dried to give 24 mg. was then added to 100 ml The precipitate was filtered dried to give 24 mg

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

Procedure: In a manner similar to Example 6, 864 mg. (0.036 mole) of 99% sodium hydride was added over a two hour period to a solution of 2.9 g. (0.015 mole) of N-methylsaccharin and 9.8 g. (0.09 mole) of methylchloroacetate in 10 ml. of dimethylsulfoxide at 40° C. Stirring was continued at 40°-45° C. for an additional two hours, and the reaction mixture was poured into 150 ml. of 5% hydrochloric acid solution. The precipitate was filtered and dried to give 3.07 (76%) of the desired product. at 40° C the reaction mixture was poured into 150 ml The precipitate was filtered dried

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

Procedure: To a solution of 2.9 g. (0.015 mole) of N-methylsaccharin and 2.63 g. (0.03 mole) of methylchloroacetate in 10 ml. of dimethylformamide at 40° C. was added over a period of two hours 864 mg. (0.036 mole) of 99% sodium hydride. Stirring was continued for two hours, maintaining a reaction temperature of 40°-50° C. The reaction mixture was quenched in 150 ml. of 5% hydrochloric acid, and the precipitated product filtered and dried, 3.41 g. (84%). maintaining a reaction temperature of 40°-50° C The reaction mixture was quenched in 150 ml of 5% hydrochloric acid, and the precipitated product filtered dried

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

Procedure: In a manner similar to Example 1B, 1.0 g. of 91% sodium hydride was added over a period of one hour to a solution of 3.0 g. (0.015 mole) of N-methylsaccharin and 2.6 g. (0.017 mole) of 2-methoxyethyl chloroacetate in 15 ml. of dimethylformamide at 35° C. The exothermic reaction (55° C.) was allowed to stir for 2 hours after the addition was complete, and was then quenched in 5% hydrochloric acid solution and the product extracted with methylene chloride. The residue, remaining after the solvent was removed, was dissolved in 10 ml. of warm dimethylformamide and added to 100 ml. of 2% hydrochloric acid. The cooled suspension was stirred for 30 minutes and filtered. Drying of the filtered material gave 1.12 g. (24%) of the product identical with that prepared in Example 1B. at 35° C The exothermic reaction (55° C.) after the addition was then quenched in 5% hydrochloric acid solution the product extracted with methylene chloride was removed was dissolved in 10 ml of warm dimethylformamide and added to 100 ml The cooled suspension was stirred for 30 minutes filtered Drying of the filtered material gave 1.12 g

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

Procedure: To a solution of 3.0 g. (0.015 mole) of N-methylsaccharin and 2.3 g. (0.015 mole) of 2-methoxyethyl chloroacetate in 15 ml. of dimethylsulfoxide at 40° C. was added 810 mg. (0.033 mole) of sodium hydride over a 2 hour period. The resulting reaction mixture was stirred for 2 hours at 40°-50° C. and was then quenched in 5% hydrochloric acid solution. The resulting suspension was extracted with methylene chloride (2×100 ml.) and the organic layers separated, combined and washed with water (50 ml.) and a brine solution (50 ml). The organic layer was dried over magnesium sulfate and concentrated to an oil, 4.1 g. The product was purified by dissolution of the residue in 5 ml. of acetone and addition of the acetone slowly to 125 ml. of 0.25 N hydrochloric acid. The suspension was allowed to stir for several hours, and was then filtered and dried 2.6 g. (55%). The product is indistinguishable from that reported in U.S. Patent Application Ser. No. 191,716, filed Sept. 29, 1980. The resulting reaction mixture was then quenched in 5% hydrochloric acid solution The resulting suspension was extracted with methylene chloride (2×100 ml.) the organic layers separated washed with water (50 ml.) The organic layer was dried over magnesium sulfate concentrated to an oil, 4.1 g The product was purified by dissolution of the residue in 5 ml of acetone and addition of the acetone slowly to 125 ml to stir for several hours was then filtered dried 2.6 g

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 590 mg. (3 mmole) of N-methylsaccharin and 1.02 g. (6 mmole) of N-(2-pyridyl)chloroacetamide in 3 ml. of dimethylformamide at 40° C. was added 250 mg. (10.3 mmole) of 99% sodium hydride portionwise over a period of one hour. The reaction mixture was allowed to stir at 40° C. for 2.5 hours and was then added to 100 ml. of 5% hydrochloric acid solution and 300 ml. of ice. The precipitate was filtered and dried to give 24 mg. was then added to 100 ml The precipitate was filtered dried to give 24 mg

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 590 mg. (3 mmole) of N-methylsaccharin and 1.02 g. (6 mmole) of N-(2-pyridyl)chloroacetamide in 3 ml. of dimethylformamide at 40° C. was added 250 mg. (10.3 mmole) of 99% sodium hydride portionwise over a period of one hour. The reaction mixture was allowed to stir at 40° C. for 2.5 hours and was then added to 100 ml. of 5% hydrochloric acid solution and 300 ml. of ice. The precipitate was filtered and dried to give 24 mg. was then added to 100 ml The precipitate was filtered dried to give 24 mg

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

Procedure: In a manner similar to Example 6, 864 mg. (0.036 mole) of 99% sodium hydride was added over a two hour period to a solution of 2.9 g. (0.015 mole) of N-methylsaccharin and 9.8 g. (0.09 mole) of methylchloroacetate in 10 ml. of dimethylsulfoxide at 40° C. Stirring was continued at 40°-45° C. for an additional two hours, and the reaction mixture was poured into 150 ml. of 5% hydrochloric acid solution. The precipitate was filtered and dried to give 3.07 (76%) of the desired product. at 40° C the reaction mixture was poured into 150 ml The precipitate was filtered dried