Triethylamine → N-(2-aminoethyl)methanesulfonamide hydrochloride

Participants

Reaction Conditions

Reaction Steps

40 g (0.392 mol) of N-(2-aminoethyl)acetamide and 59.4 g (0.587 mol) of triethylamine were dissolved in 600 ml of dichloromethane. The solution was cooled down to 0 . . . +5° C. after which 67.2 g (0.587 mol) of methanesulfonyl chloride was added during a period of 1-1.5 h under continuous stirring, while keeping the temperature not higher than +5° C. during the addition. When the addition was finished the reaction mixture was stirred for another 3 hours while the temperature was allowed to rise to room temperature. After the reaction was completed the reaction mixture was evaporated to dryness. Dichloromethane saturated with ammonia (2000 ml) was added to the evaporation residue and the mixture was triturated for 15-30 min at room temperature. The formed precipitate was filtered off and the filtrate was evaporated to dryness. The evaporation residue was dissolved in 6 M hydrochloric acid (980 ml). The solution was heated to reflux (approx. 110° C.) and stirred at this temperature for 2 h. When the reaction was finished the reaction mixture was allowed to cool down to 60° C. and then evaporated to dryness under reduced pressure. The evaporation residue was dissolved in 460 ml of methanol and then again evaporated to dryness to remove traces of water. The residue was dissolved in another 460 ml of methanol after which 3 g of −activated carbon (Norit® SX1) was added. The mixture was stirred for 15 min at 30° C., and filtered. The methanol solution was concentrated to about one third of the original mass. The crystallization was initiated by adding 85 ml of dichloromethane during 1 h under constant stirring. The solution was seeded by adding approximately 200 mg of seeding material N-(2-aminoethyl)methanesulfonamide hydrochloride. The solution was stirred for 15 min after which slow dichloromethane addition (1600 ml) was continued over a period of 6 hours under constant stirring. The mixture was cooled to 5° C. and stirred at this temperature for another 3 hours. The crystals were filtered and washed with 2×70 ml of cold acetone. The product was dried under vacuum at 30° C. overnight. The yield was typically in the range of 70-80%.

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