反应详情

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.

1. customwas quenched in phosphate buffer solution
2. extractionThe product was extracted into ethyl acetate
3. washwashed with water
4. filtrationfiltered off
5. customevaporated by vacuum
6. customto get the thick paste
7. stirringthen stirred
8. additionwas added
9. filtrationThe palladium carbon was filtered off
10. customthe organic layer separated
11. extractionThe aqueous layer was extracted with ethyl acetate
12. customthen separated
13. customby degassing
14. customto remove ethyl acetate
15. filtrationCarbon was filtered off
16. washwashed with water
17. additionTo the aqueous layer, excess THF was added
18. customto precipitate Meropenem trihydrate
19. filtrationThe product was filtered
20. washwashed with aqueous THF