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 (32 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 with ethyl acetate and washed with water. The organic layer was subjected to carbon treatment, filtered off and evaporated under vacuum to get thick paste. To the thick paste was added ethyl acetate and THF to get clear solution followed by water. This solution was washed with brine solution and the layers separated. To the reaction mass, water was added and subjected to hydrogenation with 10% palladium on carbon. The palladium carbon was filtered off and the organic layer separated. The aqueous layer was subjected to carbon treatment, filtered and washed with water. To the aqueous layer was added excess acetone to precipitate the product. The product was filtered, washed with aqueous acetone and dried to afford the title compound (22 g) as off white crystals.

Provenance & Evidence