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

HRID 571165Notes

Reaction equation

HRID 571165 reaction equation
[C:1](=[O:23])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[CH:5][CH:4]=1.[NH2:24][C@@H:25]([CH2:29][S:30]([O-:33])(=[O:32])=[O:31])[C:26]([O-:28])=[O:27].[Na+].[Na+].OC1C=CC(NC(=O)C)=CC=1.C(Cl)(=O)OC1C=CC([N+]([O-])=O)=CC=1>C(#N)C.O>[C:10]([NH:9][C:6]1[CH:5]=[CH:4][C:3]([O:2][C:1]([NH:24][C@@H:25]([CH2:29][S:30]([OH:33])(=[O:32])=[O:31])[C:26]([OH:28])=[O:27])=[O:23])=[CH:8][CH:7]=1)(=[O:12])[CH3:11]

Participants

7

Reactant 4

HCID 1983AcetaminophenHCID 821294-Nitrophenyl chloroformateHCID 594879154-Acetamidophenyl 4-nitrophenyl carbonate2×HCID 86731795Disodium (2R)-2-amino-3-sulfonato-propanoate

Product 1

HCID 86731794(2R)-2-[(4-Acetamidophenoxy)carbonylamino]-3-sulfo-propanoic acidYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

(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]+.

Workup

  1. custom(2R)-2-[(4-Acetamidophenoxy)carbonylamino]-3-sulfo-propanoic acid (13a) was prepared

Sources & evidence

ORD record
ord-6e5840d282924ce59bea9a83b2fcdea7
Source dataset
uspto-grants-2015_05
Patent number
US09024055B2

Reaction notes

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