In 10 ml of toluene were dissolved 500 mg of isobutyryloxymethyl (5R,6S,7S)-7-[(R)-1-tert-butyldimethylsilyloxymethyl]-5-methyl-4,8-dioxo-1-aza-3-thia-bicyclo-[4.2.0]octan-2-carboxylate and 277 mg of triphenylphosphine, 130 mg of potassium tert-butoxide was added thereto under nitrogen gas at -40° C. while stirring, and the mixture was stirred at the same temperature for 50 minutes. To the reaction mixture was added dropwise 10 ml of acetonitrile solution containing 312 mg of diphenyl chlorophosphate at -40° C., and the mixture was stirred for 40 minutes. To the reaction mixture were added 155 mg of (4S)-4-mercaptopyrrolidin-2-thione and 148 mg of diisopropylethylamine, and the mixture was stirred at -20° C. for 80 minutes, and then at -5° C. for 1.5 hours. The reaction mixture was poured into a 0.1M phosphate buffer (pH 7.0) and extracted with ethyl acetate. After the extract was washed and dried, the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate:chloroform=5:5:1) to obtain 248 mg of isobutyryloxymethyl (1R,5S,6S)-6-[(R)-1-tert-butyldimethylsilyloxyethyl]-2-[(4R)-pyrrolidin-2-thion-4-ylthio]-1-methylcarbapen-2-em-3-carboxylate.
