MK-0826 can be synthesized as follows: The cyclization of 2-diazo-4-[3-(1-hydroxyethyl)-4-oxoazetidin-2-yl]-3-oxopentanoic acid allyl ester (I) by means of rhodium octanoate gives the 2-oxocarbapenam derivative (II), which by reaction with chlorophosphoric acid diphenyl ester (III) and DIEA in acetonitrile yields the enol phosphate (IV). Condensation of (IV) with the sulfanylpyrrolidine (V) by means of DIEA in acetonitrile affords the corresponding addition compound MK-0826 diallyl ester (VI), which is finally deprotected by means of Meldrum's acid and Pd(PPh3)4 in DMF/THF and converted to the sodium salt.
The sulfanylpyrrolidine (V) can be obtained as follows: Esterification of 3-nitrobenzoic acid (VII) with allyl bromide and K2CO3 in DMF gives the corresponding allyl ester (VIII), which is reduced with SnCl2 in refluxing ethyl acetate to yield the 3-aminobenzoate (IX). The condensation of (IX) with the pyrrolidinecarbonyl chloride (X), obtained from the corresponding carboxylic acid (XI) and oxalyl chloride, by means of NMM in dichloro-methane affords the expected amide (XII), which is finally deacetylated with NaOH in allyl alcohol.