Phosphoric Acid → HCID 69731219, compound

HRID 1071823Notes

Reaction equation

HRID 1071823 reaction equation
C1(CC([NH:10][C@@H:11]2[C:31](=[O:32])[N:13]3[CH:14]([C:19]([O:21][CH2:22][C:23]4[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=4)=[O:20])[C:15](=[CH2:18])[CH2:16][S:17][C@H:12]23)=O)C=CC=CC=1.P(Cl)(Cl)(Cl)(Cl)Cl.OP([O-])([O-])=O.[K+].[K+].OP(O)(O)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.N[C@@H]1C(=O)N2C(C(OCC3C=CC(OC)=CC=3)=O)C(=C)CS[C@H]12>ClCCl.N1C=CC=CC=1.CO>[NH2:10][C@@H:11]1[C:31](=[O:32])[N:13]2[CH:14]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=3)=[O:20])[C:15](=[CH2:18])[CH2:16][S:17][C@H:12]12

Participants

9

Reactant 5

HCID 1004Phosphoric AcidHCID 24450Potassium Phosphate, DibasicHCID 24819Phosphorus pentachlorideHCID 10671346HCID 10671346, compoundHCID 86594250HCID 86594250, compound

Product 1

HCID 69731219HCID 69731219, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-30 °C

Procedure

To a previously cooled (−15° C.) solution of 5 g of 4-methoxybenzyl 7β-phenylacetamido-3-methylenecepham-4-carboxylate in 200 ml of anhydrous dichloromethane, 8.9 ml of anhydrous pyridine and, subsequently, 7.3 g of PCl5 are added under stirring, and stirring is continued for 1 hour at −15° C. The reaction mixture is cooled to −30° C., 55.4 ml of absolute methanol are added thereinto, the mixture is stirred 90 minutes at −15° C. then 60 minutes at 0° C. and finally 60 minuts at 25° C. To the resulting mixture, 200 ml of a 0.5 M solution of K2HPO4 are added, the the pH is adjusted to bout 2 by addition of 5% H3PO4. The mixture is let to stand 30 minutes under stirring at 25° C., then the organic phase is separated, the organic one is extracted twice with dichloromethane and the collected organic phases are dried over sodium sulfate and concentrated under reduced pressure. The obtained oily residue is dissolved in 70 ml of ethyl acetate, the solution is cooled to 0° C. and treated first with a solution of 3.15 g of p-toluene sulfonic acid monohydrate in 70 ml of ethyl acetate, then with 70 ml of diethyl ether. After standing overnight at 4° C., the precipitate is filtered to give 3.92 g of practically pure (thin layer chromatography, eluent ethyl acetate/n-hexane 7/3, Rf=0.20) 4-methoxybenzyl 7β-amino-3-methylenecepham-4-carboxylate p-toluenesulfonic acid addition salt.

Workup

  1. stirringstirring
  2. stirringthe mixture is stirred 90 minutes at −15° C.
  3. custom60 minutes
  4. customat 0° C.
  5. customat 25° C
  6. waitto stand 30 minutes
  7. stirringunder stirring at 25° C.
  8. customthe organic phase is separated
  9. extractionthe organic one is extracted twice with dichloromethane
  10. dry with materialthe collected organic phases are dried over sodium sulfate
  11. concentrationconcentrated under reduced pressure
  12. dissolutionThe obtained oily residue is dissolved in 70 ml of ethyl acetate
  13. temperaturethe solution is cooled to 0° C.
  14. additiontreated first with a solution of 3.15 g of p-toluene sulfonic acid monohydrate in 70 ml of ethyl acetate
  15. waitAfter standing overnight at 4° C.
  16. filtrationthe precipitate is filtered
  17. customto give

Sources & evidence

ORD record
ord-61fc21df574446ffa10bd6edd72e6d5a
Source dataset
uspto-grants-2005_06
Patent number
US06906187B2

Reaction notes

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