Ammonia → Benzamide, 2-(aminosulfonyl)-N,N-diethyl-4-methoxy-6-(1-methylethyl)-

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Reaction Conditions

Reaction Steps

To a solution of N,N,N',N'-tetramethylethylenediamine (300 mL) in anhydrous ether (4 L) was added s-butyllithium (1.3M, 4 L) and the mixture was cooled to -70° C. under nitrogen. A solution of 2-isopropyl-4-methoxy-N,N-diethylbenzamide (454.2 g) in anhydrous ether (300 mL) was added dropwise over 30 minutes. The temperature was maintained at or below -60° C. during the addition. After the addition the mixture was stirred at -70° C. for one hour, allowed to warm to -50° C., held at -50° C. for 30 minutes, then cooled back to -70° C. By cannulation tube a solution of sulfur dioxide (200 g) in anhydrous ether (200 mL) precooled to -40° C. was added under positive nitrogen pressure over a 20-minute period. The temperature of the reaction mixture during the addition was maintained below -40° C. A white powdery precipitate of aryllithium sulphinate separated out almost immediately. After the addition the cooling bath was removed and the mixture was stirred at ambient temperature for two hours, then cooled to -5° C. With continued stirring sulfuryl chloride (190 mL) was added dropwise over a 15-minute period while maintaining the temperature below 10° C. After further stirring for 30 minutes at 0°-5° C. a white precipitate was filtered off and washed with anhydrous ether (2 L). Removal of the solvent at atmospheric pressure gave a dark oil, which was dissolved in tetrahydrofuran (1.4 L). The solution was cooled to -10° C. and concentrated aqueous ammonia (28%, 540 mL) was added in portions over 15 minutes. The temperature was kept at 15° C. or below throughout the addition. After stirring for 15 minutes at ambient temperature the tetrahydrofuran and excess ammonia were removed under vacuum to give a dark oil, which was diluted with water (6.0 L) and acidified with hydrochloric acid (3N) to pH 1. The resulting light yellow solid was collected by filtration, washed with water (800 mL), dried at 60° C. under vacuum for 18 hours and recrystallized from ethyl acetate-hexane (800 mL-3 L) to give 2-aminosulfonyl-6-isopropyl-4-methoxy-N,N-diethylbenzamide (429 g, 72% yield, m.r. 122°-125° C.).

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