Hydrochloric Acid → Meropenem

HRID 78679Notes

Reaction equation

HRID 78679 reaction equation
O(P(O[C:18]1[C@H:24]([CH3:25])[C@H:23]2[N:20]([C:21](=[O:29])[C@@H:22]2[C@H:26]([OH:28])[CH3:27])[C:19]=1[C:30]([O:32]CC1C=CC([N+]([O-])=O)=CC=1)=[O:31])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[CH3:43][N:44]([CH3:66])[C:45]([C@@H:47]1[CH2:51][C@H:50]([SH:52])[CH2:49][N:48]1C(OCC1C=CC([N+]([O-])=O)=CC=1)=O)=[O:46].C(N(C(C)C)CC)(C)C.CN1CCOCC1.Cl>CN1CCCC1=O.O.[C].[Pd]>[CH3:25][C@H:24]1[C:18]([S:52][C@@H:50]2[CH2:49][NH:48][C@H:47]([C:45]([N:44]([CH3:66])[CH3:43])=[O:46])[CH2:51]2)=[C:19]([C:30]([OH:32])=[O:31])[N:20]2[C@H:23]1[C@@H:22]([C@H:26]([OH:28])[CH3:27])[C:21]2=[O:29]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 81531DiisopropylethylamineHCID 10304013(4-nitrophenyl)methyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylateHCID 10871907(2S,4S)-2-(dimethylaminocarbonyl)-4-mercapto-1-(p-nitrobenzyloxycarbonyl)-1-pyrrolidine

Product 1

HCID 441130Meropenem

Reagents, catalysts & solvents 3

HCID 178418390HCID 178418390, compoundCatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-nitrobenzyl (4R,5R,6S)-3-[(diphenoxyphosphoryl)oxy]-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (Formula VIIIA; 20 g) was dissolved in N-methyl-2-pyrrolidone (100 mL) and cooled to −20° to −15° C. 4-Nitrobenzyl (2S,4S)-2-[(dimethylamino)carbonyl]-4-mercaptopyrrolidine-1-carboxylate (12 g) was added to the reaction mixture followed by the drop-wise addition of diisopropylethylamine (5.6 g) at −15° to −5° C. and the reaction mixture was stirred. The reaction mixture was subsequently added to a buffer containing 5% palladium-carbon (30 g) and hydrogenated for 3 to 4 hours at about 25° C. (The buffer was prepared using N-methylmorpholine (3.4 g) and appropriate quantity of hydrochloric acid so as to obtain a pH of 6.5 to 7.0 in distilled water (120 mL)). The catalyst was filtered after the completion of hydrogenation and washed with water (100 mL). The filtrate was treated with activated charcoal and acetone (1.6 L) was added to the filtrate at 0° to 5° C. The reaction mixture was stirred for 6 hours at 0° to 5° C. and filtered to obtain the title compound.

Workup

  1. temperaturecooled to −20° to −15° C
  2. additionThe reaction mixture was subsequently added to
  3. customhydrogenated for 3 to 4 hours at about 25° C. (The buffer was prepared
  4. filtrationThe catalyst was filtered after the completion of hydrogenation
  5. washwashed with water (100 mL)
  6. additionThe filtrate was treated with activated charcoal and acetone (1.6 L)
  7. additionwas added to the filtrate at 0° to 5° C
  8. stirringThe reaction mixture was stirred for 6 hours at 0° to 5° C.
  9. filtrationfiltered

Sources & evidence

ORD record
ord-013d7b6537bc448c84a1e28f02e8d895
Source dataset
uspto-grants-2014_09
Patent number
US08841444B2

Reaction notes

Loading…