synthesis method of dl-2-amino-3-phosphopropionic acid_industrial additives

background and overview^[1]

dl-2-amino-3-phosphopropionic acid is a nitrogen-containing organophosphorus compound. nitrogen-containing organophosphorus compounds have a wide range of biological activities and have important applications in anti-hypercalcemia, anti-hiv virus, antibacterial and as enzyme inhibitors; in addition, β-phosphoryl oxime free radical compounds can also be used in biomolecules mark.

preparation^[1]

using ethyl acrylate and diethyl phosphite as raw materials, the reaction steps are as follows:

(1) add ethyl acrylate (0.040 g, 0.4 mmol), diethyl phosphite (0.055 g, 0.4 mmol), tert-butyl nitrite (0.041 g, 0.4 mmol), nitric acid into the reaction bottle silver (0.07g, 0.04 mmol), water (1 ml) and ethanol (1.5 ml), reaction at room temperature;

(2)tlc follows the reaction until it is completely completed;

(3) the crude product obtained after the reaction was separated by column chromatography (ethyl acetate:petroleum ether = 1:1) to obtain compound 32-1 (yield 71%). the analytical data of the product are as follows: 1h nmr (mhz, cdcl3): δ 10.73 (s, 1 alcohol h), 3.99 – 3.87 (m, 6h), 3.63 (d, j = 23.3 hz, 2h), 1.16-1.03 ( m, 9h);

(4) add 2 ml of methanol solution of nickel (0.058 g, 0.1 mmol) and compound 32-1 (0.267 g, 1 mmol) into the reaction bottle. at room temperature, add sodium hydroxide aqueous solution dropwise to the solution ( 2 ml, 5.0 m) and sodium borohydride (0.12 g, 3 mmol) in methanol solution (2 ml), complete the dropwise addition in 2 hours, react at room temperature for 3 hours, filter, and neutralize the solution with concentrated hydrochloric acid to ph≈9, acetic acid extract with ethyl ester (3×5 ml), dry over anhydrous na2so4, distill, and concentrate. the crude clariant pigment product is separated by column chromatography (ethyl acetate:petroleum ether = 1:1) to obtain compound 32-2 (yield 80%). the analytical data of the product are as follows: 1h nmr (300mhz, cdcl3): δ 3.99 – 3.87 (m, 7h), 3.63 (dd, j = 23.3, 7.0 hz, 2h), 1.61 (s,2h), 1.16 – 1.03 (m , 9h);

(5) add 32-2 (0.253 g, 1 mmol) and concentrated hydrochloric acid (20 ml) to the reaction flask, heat and reflux until the reaction is complete, add 50 ml of water, extract with dichloromethane, concentrate and dry , the crude product was recrystallized with ethanol/water to obtain the target product c1 (yield 84%). the analytical data of the product are as follows: 1h nmr (300 mhz, cdcl3): δ 16.90 (s, 1h), 8.76 (s, 2h), 4.80 (s, 2h), 3.63 (dd, j = 23.3, 6.8 hz, 2h) , 3.46-3.39 (m, 1h);