Ethyl Acetate → Meropenem Trihydrate

Participants

Reaction Steps

To a solution of (4R,5R,6S)-3-[(diphenoxyphosphoryloxy]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (4-nitrophenyl)methyl ester (50 g) in acetonitrile (500 mL) was added (2S,4S)-1-p-nitrobenzyloxycarbonyl-2-dimethylaminocarbonylamino-4-mercaptopyrrolidine (33 g) and N-ethyldiisopropylamine (14 g) at −15° C. and stirred. After the reaction was over, the reaction mixture was quenched in phosphate buffer solution. The product was extracted into ethyl acetate and washed with water. The organic layer was subjected to carbon treatment, filtered off and evaporated by vacuum to get the thick paste. To the thick paste was added THF then stirred to get clear solution and water was added thereafter. The reaction mass was subjected to hydrogenation with 10% palladium on carbon (50 g) with 9-10 kg hydrogen pressure. After the hydrogenation, ethyl acetate (500 mL) was added to reaction mixture. The palladium carbon was filtered off and the organic layer separated. The aqueous layer was extracted with ethyl acetate then separated. Then aqueous layer was charcoalised followed by degassing to remove ethyl acetate. Carbon was filtered off and washed with water. To the aqueous layer, excess THF was added to precipitate Meropenem trihydrate. The product was filtered and washed with aqueous THF to afford the title compound (22 g) as off-white crystals with 98% purity.

Provenance & Evidence