Janak Singh, O. Kim, T. P. Kissick
Sep 15, 2000
Citations
0
Influential Citations
10
Citations
Journal
Organic Process Research & Development
Abstract
A practical synthesis of the anti-methicillin resistant Staphylococcus aureus cephem (6R-trans)-E-7-[[[[2,5-dichloro-4-[3-[(carboxymethyl)amino]-3-oxo-1-propenyl]phenyl]-thio]-acetyl]amino]-4-[[(2-carboxy-8-oxo-5-thia-1-azabicyclo-[4.2.0]oct-2-en-3-yl)methyl]thio]-2,6-dimethyl-1-[3-(4-methylmorpholino-4-yl)propyl]-1-pyridinium, hydroxide, inner salt (BMS-247243) was developed. A process was developed for the interchange of the iodide counterion in 3a to chloride 3b that was essential for an efficient synthesis of the C-3 side chain 4-mercaptopyridone 6b. Use of catalytic Bu4NCl in the reaction of chlorocinnamide 14 with the Li-salt of methylthioglycolate formed the methyl ester of the C-7 side chain 12b in high yield. Reaction with the dianion of thioglycolic acid gave an increased level of the corresponding Michael addition byproduct that led to lower quality thermodynamic product 12b by the reverse reaction. Cephem nucleus 16 was acylated with the acid chloride of acid 12b in a biphasic system to circum...