Triethylamine → 2-{3-[((S)-1-Dimethylaminomethyl-3,3-dimethyl-butylamino)-methyl]-benzyl}1,1-dioxo-1lambda6-isothiazolidine-3-carboxylic acid ethyl ester

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Reaction Steps

To a stirred solution of (S)-4,4,N1,N1-tetramethyl-pentane-1,2-diamine hydrochloride salt (Intermediate 2, 0.921 g, 4.73 mmol) in methanol (10 mL) cooled in an ice bath (0° C.) was added triethylamine (2.19 mL, 15.7 mmol) and the solution was stirred at this temperature for 25 minutes. To this cooled solution was added 2-(3-formyl-benzyl)-1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester (0.937 g, 3.15 mmol) in methanol (35 mL) after which the solution was allowed to warm to room temperature and stirred for 2 hours. The solution was cooled to 0° C. and sodium cyanoborohydride (0.461 g, 7.3 mmol) and acetic acid (4 mL) were added and the solution was allowed to warm to room temperature and stirred overnight. The reaction was then concentrated under reduced pressure, partitioned between dichloromethane and saturated aqueous sodium bicarbonate and the layers were separated. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to provide crude 2-{3-[((S)-1-Dimethylaminomethyl-3,3-dimethyl-butylamino)-methyl]-benzyl}1,1-dioxo-1λ6-isothiazolidine-3-carboxylic acid ethyl ester, which was carried on to the next step without further purification.

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