Uses
(5-Methyl-2-oxo-1,3-dioxol-4-YL)methyl 4-nitrophenyl carbonate is a pharmaceutical intermediate compound for the preparation of Ceftobiprole medocaril, a broad-spectrum, 5th generation cephalosporin with activity against gram-positive bacteria (e.g. methicillin-resistant).
Synthesis
(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-nitrophenyl carbonate is prepared by the reaction of 4-Nitrophenyl chloroformate and Bis(4-nitrophenyl) carbonate. The specific synthesis steps are as follows:
4-Hydroxymethyl-5-methyl-1,3-doxolene-2-one (5.59 g) and pyridine (3.74 g) were dissolved in 50 mL of chloroform and cooled in an ice bath. 4-Nitrophenylchloroformate (9.46 g) dissolvedin chloroform (50 mL) was added dropwise to the above solution.
The mixture was stirred for 16 hours at room temperature.
The reaction mixture was cooled in ice and washed with ice cold 1percent sodium hydroxide, 1N hydrochloric acid, water and brine and dried over sodium sulfate.
Evaporation of the organic layer resulted in 11.2 g of crude product, which was crystallized from chloroform/hexane.
The crystals formed were filtered and washed with ice cold hexane/chloroform (1:1), to obtain the pure 4-nitrophenyl carbonate (9.11 g, 81percent); mp 116°-117°; 1 H NMR (CDCl3) δ2.23 (s, 3H), 5.05 (s,2H), 7.41 (d, 2H), 8.3 (s, 2H); 13 C NMR (CDCl3), δ9.43, 58.07, 121.69, 121.35, 132.15, 141.42, 145.57, 151.66, 152.19, 155.05; IR (KBr) 1779, 1811, 1525, 1247, 1221, 1207 cm-1.
