(-)-Asparagine → (S)-4-Amino-4-oxo-2-(((quinolin-2-yl)carbonyl)amino)butanoic acid

Participants

Reaction Conditions

Reaction Steps

34.60 g (200 mmol) of quinoline-2-carboxylic acid (Benechim S. A.) were suspended in 350 ml of ethyl acetate (Fluka) while stirring and under a protective gas at 0 to 5° C. and treated with 25.0 ml (200 mmol) of pivaloyl chloride (Fluka). 28.0 ml (200 mmol) of triethylamine (Fluka) were added to the white suspension within 30 minutes, with the temperature being held at 0 to 5° C. Subsequently, the suspension was stirred at 0 to 5° C. for 30 minutes. The white suspension was filtered and the filter cake was washed with 100 ml of cooled (0-5° C.) ethyl acetate (Fluka). The filtrate contained the resulting 2,2-dimethylpropionic acid-quinoline-2-carboxylic acid anhydride having the following characteristics: melting point: 47° C.; MS: [M+H]+258; IR: 1750 cm−1, 1775 cm−1. The cooled (0−-5° C.), light yellow filtrates were combined and treated within 5 minutes while stirring intensively with a pre-cooled solution of 30.0 g (200 mmol) of L-asparagine (Fluka), 8.0 g (200 mmol) of sodium hydroxide (Fluka) and 16.80 g (200 mmol) of sodium bicarbonate in 350 ml of cold, deionised water (0-5° C.), with the temperature being held at between 0 and 5° C. Subsequently, the cooling was removed and the light green two-phase system was stirred at room temperature for about 17 hours. The aqueous phase of the now colourless two-phase system was treated with 200 ml of methanol (Merck) while stirring and under argon. Then, 49 ml of 25% hydrochloric acid (Merck) were added dropwise to pH 3.0. In so doing, the temperature rose to 28° C. and crystallization set in. The white suspension was stirred at room temperature for one hour, subsequently cooled to 0-5° C. and stirred at this temperature for a further hour. The filtered-off filter cake was washed with a total of 80 ml of cold, deionised water (0-5° C.) and dried in a rotary evaporator at 5° C./10 mbar for 6 hours. Yield: 47.52 g (83%) of N-(2-quinolylcarbonyl)-L-asparagine in the form of white crystals [melting point: 209° C. (decomposition), HPLC analysis 99.8% (area)].

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