Acetaminophen → (2R)-2-[(4-Acetamidophenoxy)carbonylamino]-3-sulfo-propanoic acid

Participants

Reaction Steps

(2R)-2-[(4-Acetamidophenoxy)carbonylamino]-3-sulfo-propanoic acid (13a) was prepared according to the General Method for the Reaction of Alkali Metal Salts of Amino Acid Derivatives with 4-Acetamidophenyl 4-Nitrophenyl Carbonate (3). A solution of 500 mg (2.35 mmol) of disodium (2R)-2-amino-3-sulfonato-propanoate (9) in approximately one (1) mL of water was reacted with a solution of 4-acetamidophenyl 4-nitrophenyl carbonate (3) (844 mg, 2.67 mmol) dissolved in 5 mL of acetonitrile (MeCN). The mixture was heated to about 55° C. for two (2) hours. After work-up procedures, the aqueous layer was lyophilized off to afford 400 mg (43% yield) of the crude 2-[(4-acetamidophenoxy)carbonylamino]-3-sulfo-propanoic acid (13a). The material thus obtained was contaminated with some sodium chloride (NaCl) and other sodium salts. The crude product was further purified by preparative HPLC using a gradient consisting of acetonitrile and water containing 0.1 vol-% of formic acid. Samples eluting at 2% acetonitrile and 98% water were collected, frozen, and lyophilized off to afford 83 mg (9% yield) the target compound (13a) as a colorless solid. Rt=3.10 min. 1H NMR (300 MHz, D2O): δ=7.25 (d, J=9.0 Hz, 2H), 6.99 (d, J=9.0 Hz, 2H), 4.54-4.50 (m, 1H), 3.32-3.27 (m, 2H), 1.98 (s, 3H). LC/MS (ESI): m/z=347.0 [M+H]+, 714.8 [2M+Na]+.

Provenance & Evidence