Triethylamine → methyl (S)-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methoxyethoxymethoxy)benzoyl-amino]propanoate

Participants

Reaction Steps

1.1 g (5 mmol) of 4-(2-methoxyethoxymethoxy)benzoic acid are put into solution in 15 ml of dimethylformamide then 0.7 g (5.5 mmol) of 1-hydroxybenzotriazole and 1.1 g (5.5 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride are added. The reaction medium is stirred for 20 minutes before adding a mixture of 1.5 g (5 mmol) of methyl (S)-3-amino-2-(4-methanesulphonylpiperazin-1-yl)propanoate hydrochloride (prepared as described in 2-3) and of 1.4 ml (9.9 mmol) of triethylamine in 15 ml of dimethylformamide. The reaction medium is stirred at 50° C. for 1 h 30 min then at ambient temperature for 18 h. After hydrolysis with a saturated aqueous solution of sodium hydrogen carbonate then extraction with ethyl acetate, the organic phase is washed with an aqueous solution of sodium hydrogen carbonate then with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, filtered and concentrated. The crude product obtained is purified by chromatography over silica gel eluted with a 9/1 dichloromethane/methanol mixture. 1.6 g (68%) of methyl (S)-2-(4-methanesulphonylpiperazin-1-yl)-3-[4-(2-methoxyethoxymethoxy)benzoylamino]propanoate are obtained in the form of a colourless oil.

Provenance & Evidence