ACETAMINOPHEN GLUCURONIDE SODIUM SALT synthesis

Yield: 85%

Reaction Conditions:

Stage #1:methyl <4-(acetamido)phenyl 2,3,4-tri-O-acetyl-β-D-glucopyranosid>uronate with water in tetrahydrofuran;methanol at 0;Inert atmosphere;
Stage #2: with potassium carbonate in tetrahydrofuran;methanol at 40; for 5 h;Inert atmosphere;Further stages;

Steps:

1.2.5. 4-Acetomidophenyl-β-d-glucopyranosiduronic acid (5) sodium salt
Methyl (4-acetamidophenyl 2,3,4-tri-O-acetyl-β-d-glucopyranosid)uronate (4) (1.00 g, 2.15 mmol) was dissolved in a solution of MeOH-THF-H₂O (5:5:1, 40-50 mL) and the solution stirred under an N₂ atmosphere at 0 °C. K₂CO₃ (0.6 g, 4.3 mmol) was added and the reaction mixture was heated to 40 °C for 5 h. The reaction mixture was cooled to room temperature and neutralised with strongly acidic ion-exchange resin (Amberlyst 15 H⁺ Form). The exchange resin was removed and the solution was clarified with charcoal. After removal of the charcoal on a bed of Celite the solvent was removed and the residue was dissolved in MeOH (50 mL). aq NaHCO₃ solution (20 ml) was added and the solution heated to boiling. After heating for 10 min the solution was allowed to cool to room temperature and left to stir for 1 h. The resulting solid was isolated and recrystallised from aq EtOH to give the product as a white crystalline solid 0.63 g (85% yield). Mp 220-230 °C, (decomp.). IR (KBr) ν 3298 (O-H), 2935 (C-H), 1578 (CO), 1510 (CC), 1414 (CC), 1043 (C-O) cm^-1; ¹H NMR (D₂O) δ 7.36 (d, 2H, J 9.2 Hz, Ar-H), 7.14 (d, 2H, J 9.2 Hz, Ar-H), 5.10 (d, 1H, J 6.8 Hz, H-1), 3.89 (d, 1H, J 9.6 Hz, H-5), 3.64-3.55 (m, 3H, H-2, 3, 4), 2.16 (s, 3H, NAc).

References:

Hayes, John A.;Eccles, Kevin S.;Lawrence, Simon E.;Moynihan, Humphrey A. [Carbohydrate Research,2012,vol. 349,p. 108 - 112] Location in patent:experimental part