2-Amino-4-phosphonobutyric acid → HCID 25102185, compound

Participants

Reaction Conditions

Reaction Steps

After 24.0 g (600 mmol) of sodium hydroxide and 36.6 g (200 mmol) of 2-amino-4-phosphonobutanoic acid were dissolved in a two-layer system solvent mixture of 200 mL of water and 150 mL of ether, 51.2 g (300 mmol) of benzyl chloroformate and 25.2 g (300 mmol) of sodium hydrogen carbonate were added portionwise over 1 hour while being vigorously stirred at 0° C. After the mixture was vigorously stirred at room temperature for 14 hours, it was confirmed that the reaction was finished on the basis of disappearance of 2-amino-4-phosphonobutanoic acid by ninhydrin coloration of thin layer chromatography (TLC) (BuOH/AcOH/H2O=5:2:2). Thereafter, the water layer was separated and washed with 200 mL of ether three times successively, and the solution was acidified by adding 140 mL (840 mmol) of theoretical amount of 6N hydrochloric acid. The aqueous solution was concentrated in reduced pressure, 500 mL of acetone was added to the residue, and insoluble sodium chloride was removed by filtration. The filtrate was concentrated to obtain oily 2-(N-benzyloxycarbonylamino)-4-phosphonobutanoic acid as a crude product. To the crude product, was added 250 mL of an aqueous solution containing 7.2 g (180 mmol) of sodium hydroxide proper for neutralization to adjust the pH to about 3 and the aqueous solution was evaporated to dryness under reduced pressure. The obtained oily substance was mixed with acetone and kept still to obtain 2-(N-benzyloxycarbonylamino)-4-phosphonobutanoic acid monosodium salt (51.8 g, yield 76%) as white powder-like crystals.

Provenance & Evidence