Ethyl Acetate → Meropenem Trihydrate

HRID 1685969Notes

Reaction equation

HRID 1685969 reaction equation
[N+](C1C=CC(C[O:11][C:12]([C:14]2[N:15]3[CH:18]([CH:19]([CH3:38])[C:20]=2OP(OC2C=CC=CC=2)(OC2C=CC=CC=2)=O)[CH:17]([C@H:39]([OH:41])[CH3:40])[C:16]3=[O:42])=[O:13])=CC=1)([O-])=[O:2].[N+](C1C=CC(COC([N:54]2[CH2:58][C@@H:57]([SH:59])[CH2:56][C@H:55]2NC(N(C)C)=O)=O)=CC=1)([O-])=[O:44].[CH2:68]([N:70]([CH:74](C)C)[CH:71](C)C)C.C(OCC)(=[O:79])C>C(#N)C.O.C1COCC1>[CH3:38][C@H:19]1[C:20]([S:59][C@@H:57]2[CH2:58][NH:54][C@H:55]([C:68]([N:70]([CH3:74])[CH3:71])=[O:79])[CH2:56]2)=[C:14]([C:12]([OH:11])=[O:13])[N:15]2[C@H:18]1[C@@H:17]([C@H:39]([OH:41])[CH3:40])[C:16]2=[O:42].[OH2:2].[OH2:44].[OH2:2]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 66686211(diphenoxyphosphoryloxy]-6-[(R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (4-nitrophenyl)methyl esterHCID 87330369(2s,4s)-1-p-Nitrobenzyloxycarbonyl-2-dimethylaminocarbonylamino-4-mercaptopyrrolidine

Product 1

HCID 441129Meropenem Trihydrate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  1. customwas quenched in phosphate buffer solution
  2. extractionThe product was extracted with ethyl acetate
  3. washwashed with water
  4. filtrationfiltered off
  5. customevaporated under vacuum
  6. customto get thick paste
  7. customto get clear solution
  8. washThis solution was washed with brine solution
  9. customthe layers separated
  10. additionTo the reaction mass, water was added
  11. filtrationThe palladium carbon was filtered off
  12. customthe organic layer separated
  13. filtrationfiltered
  14. washwashed with water
  15. additionTo the aqueous layer was added excess acetone
  16. customto precipitate the product
  17. filtrationThe product was filtered
  18. washwashed with aqueous acetone
  19. customdried

Sources & evidence

ORD record
ord-67a18ef9b81649cbaec3799a40348f13
Source dataset
uspto-grants-2012_04
Patent number
US08148520B2

Reaction notes

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