Potassium Chloride → ethyl (2R)-2-(acetylamino)-3-(3-pyridyl)propanoate

Participants

Reaction Steps

A suspension of 54.7 g of ethyl 2-(acetylamino)-3-(3-pyridyl)propanoate in 420 cm3 of water, to which has been added 18.5 g of potassium chloride, is dissolved by adding 100 cm3 of acetonitrile. An orange-colored solution of neutral pH is obtained, 0.168 g of α-chymotrypsin is then added and the pH falls. Aqueous 2N potassium hydroxide solution is added dropwise, with stirring, to remain at a constant pH of 7.2. After 1 hour 30 min, with the pH showing little change, the mixture is stirred for 48 hours at room temperature. The pH of the solution is then approximately 5.6 and, on adding aqueous 2N potassium hydroxide solution, it is thereby adjusted to about 7. 0.084 g of α-chymotrypsin is introduced and the pH is adjusted to 7.2 by a further addition of aqueous 2N potassium hydroxide solution, and the mixture is left stirring for 1 hour 30 min. The pH of the reaction medium does not change. 400 cm3 of ethyl acetate are added and the mixture is stirred for 30 min and then filtered through Celite. The filtrate is separated out after settling has taken place and the aqueous phase is extracted with 3 times 400 cm3 of ethyl acetate. The organic phases are combined, washed with 400 cm3 of saturated sodium chloride solution and dried over magnesium sulfate. After filtration and concentration under reduced pressure (2 kPa) at a temperature in the region of 40° C., 20.77 g of ethyl (2R)-2-(acetylamino)-3-(3-pyridyl)propanoate are obtained in the form of a beige-colored solid melting at 80° C. [1H NMR spectrum (400 MHz, (CD3)2SO-d6, δ in ppm): 1.13 (t, J=7 Hz: 3H); 1.81 (s: 3H); 2.92 (dd, J=14 and 9.5 Hz: 1H); 3.05 (dd, J=14 and 5.5 Hz 1H); 4.07 (q, J=7 Hz: 2H); 4.48 (mt: 1H); 7.33 (dd, J=8 and 5 Hz: 1H); 7.66 (dt, J=8 and 2 Hz: 1H); 8.36 (d, J=8 Hz: 1H); 8.44 (mt: 2H)].

Provenance & Evidence