Acetamide, 2-(trimethylsilyl)- → HCID 131714487, compound

HRID 1907032Notes

Reaction equation

HRID 1907032 reaction equation
[OH2:1].[OH2:2].Cl.Cl.[NH2:5][CH:6]1[C:23](=[O:24])[N:8]2[C:9]([C:20]([O-:22])=[O:21])=[C:10]([CH2:13][N+:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:11][S:12][C@H:7]12.C[Si](CC(N)=O)(C)C.[CH2:33]([O:36][N:37]=[C:38]([C:42]1[N:46]=[C:45]([NH:47][P:48](Cl)(Cl)=[O:49])[S:44][N:43]=1)[C:39](Cl)=[O:40])[CH:34]=[CH2:35].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH2:33]([O:36][N:37]=[C:38]([C:42]1[N:46]=[C:45]([NH:47][P:48]([OH:49])([OH:2])=[O:1])[S:44][N:43]=1)[C:39]([NH:5][CH:6]1[C:23](=[O:24])[N:8]2[C:9]([C:20]([O-:22])=[O:21])=[C:10]([CH2:13][N+:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:11][S:12][C@H:7]12)=[O:40])[CH:34]=[CH2:35]

Participants

6

Reactant 4

HCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 53908142HCID 53908142, compoundHCID 67897133HCID 67897133, compound

Product 1

HCID 131714487HCID 131714487, compoundYield 74.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 7-amino-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate dihydrochloride dihydrate (56 g) in methylene chloride (1.12 l) was added trimethylsilylacetamide (280 g) and the mixture was stirred for 15 minutes at ambient temperature. The solution was cooled at -20° C. and 2-allyloxyimino-2-(5-dichlorophosphorylamino-1,2,4-thiadiazol-3-yl)acetyl chloride (syn isomer) (51 g) was added thereto at the same temperature under stirring, which was continued for 20 minutes at -13° to -10° C. and for 30 minutes at -5° to 0° C. The reaction mixture was poured into a saturated aqueous solution of sodium bicarbonate (1 l) under stirring and the aqueous layer was separated out. The organic layer was extracted twice with water (800 ml, 400 ml) and the extracts were combined with the aqueous layer. The combined aqueous solution was adjusted to pH 1.5 with 6N hydrochloric acid and the resulting precipitate was filtered off. The filtrate was subjected to column chromatography on nonionic adsorption resin "Diaion HP-20" (6 l). After the column was washed with water (10 l), the elution was carried out with 20% aqueous methanol. The fractions containing the object compound were combined, adjusted to pH 6.0 with 1N aqueous sodium hydroxide and concentrated to a weight of 318 g under reduced pressure. To the solution was added ion-exchange resin "Dowex 50 W 10 X (H+ form)" (prepared by the Dow Chemical Co.) (120 g) and the mixture was stirred for 5 minutes. The resin was filtered off, washed with water (142 ml), and the filtrate and the washings were combined. The combined solution was mixed with n-butanol (2.5 l) at -15° to -10° C. and to the resulting solution was added acetone (2.5 l) dropwise at -10° C. under stirring, which was continued for 40 minutes after removing the cooling bath. The resulting precipitate was filtered, washed with acetone (500 ml) and dried to give 7-[2-allyloxyimino-2-(5-phosphonoamino-1,2,4-thiadiazol-3-yl)acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer) (60.6 g), mp. 175° to 181° C. (dec.).

Workup

  1. temperatureThe solution was cooled at -20° C.
  2. stirringat the same temperature under stirring
  3. waitwhich was continued for 20 minutes at -13° to -10° C. and for 30 minutes at -5° to 0° C
  4. stirringunder stirring
  5. customthe aqueous layer was separated out
  6. extractionThe organic layer was extracted twice with water (800 ml, 400 ml)
  7. filtrationthe resulting precipitate was filtered off
  8. washAfter the column was washed with water (10 l)
  9. washthe elution
  10. additionThe fractions containing the object compound
  11. concentrationconcentrated to a weight of 318 g under reduced pressure
  12. additionTo the solution was added ion-exchange resin "Dowex 50 W 10 X (H+ form)" (
  13. customprepared by the Dow Chemical Co
  14. stirring) (120 g) and the mixture was stirred for 5 minutes
  15. filtrationThe resin was filtered off
  16. washwashed with water (142 ml)
  17. additionThe combined solution was mixed with n-butanol (2.5 l) at -15° to -10° C. and to the resulting solution
  18. additionwas added acetone (2.5 l) dropwise at -10° C.
  19. stirringunder stirring
  20. waitwhich was continued for 40 minutes
  21. customafter removing the cooling bath
  22. filtrationThe resulting precipitate was filtered
  23. washwashed with acetone (500 ml)
  24. customdried

Sources & evidence

ORD record
ord-cf74e6c5c5954f268258791ab3bc5623
Source dataset
uspto-grants-1987_03
Patent number
US04654422

Reaction notes

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