Hydrochloric Acid → HCID 131714485, compound

HRID 1284580Notes

Reaction equation

HRID 1284580 reaction equation
[CH2:1]([O:4][N:5]=[C:6]([C:10]1[N:14]=[C:13]([NH:15][P:16]([O:20][CH3:21])([O:18][CH3:19])=[O:17])[S:12][N:11]=1)[C:7]([O-:9])=O)[CH:2]=[CH2:3].[Na+].C(=O)(O)[O-].[Na+].CS(Cl)(=O)=O.Cl.Cl.[NH2:35][CH:36]1[C:53](=[O:54])[N:38]2[C:39]([C:50]([O-:52])=[O:51])=[C:40]([CH2:43][N+:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH2:41][S:42][C@H:37]12.C[Si](CC(N)=O)(C)C.Cl>CN(C)C(=O)C.C(Cl)Cl>[CH2:1]([O:4][N:5]=[C:6]([C:10]1[N:14]=[C:13]([NH:15][P:16]([O:20][CH3:21])([O:18][CH3:19])=[O:17])[S:12][N:11]=1)[C:7]([NH:35][CH:36]1[C:53](=[O:54])[N:38]2[C:39]([C:50]([O-:52])=[O:51])=[C:40]([CH2:43][N+:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH2:41][S:42][C@H:37]12)=[O:9])[CH:2]=[CH2:3]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 31297Methanesulfonyl chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium Bicarbonate2×HCID 67897138HCID 67897138, compoundHCID 74088770HCID 74088770, compound

Product 1

HCID 131714485HCID 131714485, compoundYield 62.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-30 °C

Procedure

To a suspension of sodium 2-allyloxyimino-2-[5-dimethoxyphosphorylamino-1,2,4-thiadiazol-3-yl]acetate (syn isomer) (358.5 mg) and sodium bicarbonate (42 mg) in N,N-dimethylacetamide (3.6 ml) was added dropwise methanesulfonyl chloride (172 mg) under cooling in an ice bath and stirring, which was continued for 1.5 hours at the same temperature. On the other hand, a mixture of 7-amino-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate dihydrochloride (400 mg) and trimethylsilylacetamide (2 g) in methylene chloride (4 ml) was stirred at room temperature to give a solution and cooled to -30° C. The cold solution was added to the activated mixture prepared above and the resulting mixture was stirred for 30 minutes at -20° to -15° C. and then for additional 20 minutes at -15° to 0° C. The mixture was poured into 6% aqueous solution of sodium bicarbonate (5 ml), adjusted to pH 3 with 6N hydrochloric acid and evaporated to remove methylene chloride. The residual aqueous solution was diluted to 72 ml with water and subjected to column chromatography on a nonionic adsorption resin "Diaion HP-20" (Trademark: prepared by Mitsubishi Chemical Industries) (36 ml). After the column was washed with water, the elution was carried out with 30% and 40% aqueous methanol successively. The fractions containing the object compound were collected, evaporated to remove methanol under reduced pressure and lyophilized to give 7-[2-allyloxyimino-2-{5-dimethoxyphosphorylamino-1,2,4-thiadiazol-3-yl}acetamido]-3-(1-pyridiniomethyl)-3-cephem-4-carboxylate (syn isomer) 379 mg), mp. 157° to 165° C. (dec.).

Workup

  1. temperatureunder cooling in an ice bath
  2. stirringwas stirred at room temperature
  3. customto give a solution
  4. additionThe cold solution was added to the activated mixture
  5. customprepared above and the resulting mixture
  6. stirringwas stirred for 30 minutes at -20° to -15° C.
  7. waitfor additional 20 minutes at -15° to 0° C
  8. customevaporated
  9. customto remove methylene chloride
  10. additionThe residual aqueous solution was diluted to 72 ml with water
  11. custom" (Trademark: prepared by Mitsubishi Chemical Industries) (36 ml)
  12. washAfter the column was washed with water
  13. washthe elution
  14. additionThe fractions containing the object compound
  15. customwere collected
  16. customevaporated
  17. customto remove methanol under reduced pressure

Sources & evidence

ORD record
ord-4e2f5571f1c64d2089b0a68e584f4a0d
Source dataset
uspto-grants-1986_01
Patent number
US04563449

Reaction notes

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