Methyl Chloroformate

A Facile Synthesis of Raltegravir Potassium—An HIV Integrase Inhibitor

“…Michael addition between 4 to dimethyl acetylenedicarboxylate (DMAD) and subsequent thermal rearrangement afforded 2-(1-methyloxycarbonylamino-1-methyl-ethyl)-5-hydroxy -6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid methy lester (6). Coupling reaction of 6 with 4-fluoroben zylamine in the presence of triethylamine produced N-[(4fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-2-[(1-methyl -1-[[(methoxy)carbonyl]amino]ethyl-6-oxo-4-pyrimidine carboxamide (7). (9).…”

“…In support of that, several protecting reagents were tested including MOC, ethylchloroformate, di-tert-butyl dicarbonate, and fluorenylmethyloxycarbonylchloride that could eliminate the hydrogenation. Among these, we chose commercially inexpensive MOC [7] as a protecting reagent for amino group in 2. After selecting the suitable protecting reagent, we studied different suitable base reagents including diisopropyl amine, triethylamine, sodium carbonate, and sodium hydroxide.…”

“…Purity by HPLC: 99%, mp: 218-219°C. 1 oxo-4-pyrimidine carboxamide (7). To a suspension of 6 (200 g, 0.701 mol) in methanol (320 L), triethylamine (78 g, 0.771 mol) followed by 4-fluorobenzylamine (97 g, 0.771 mol) were added slowly portionwise for 30-40 min.…”