Hydrochloric Acid → HCID 178477399, compound

HRID 2286483Notes

Reaction equation

HRID 2286483 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][C@@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:22]([O-:24])=[O:23])=[C:14](COC(=O)C)[CH2:15][S:16][C@H:11]12)=[O:8].[Na+].Cl[Si:29]([CH3:32])([CH3:31])[CH3:30].C[Si](I)(C)C.C1O[CH:39]1[CH3:40].C[N:43]1[C:47]([SH:48])=[N:46][N:45]=[N:44]1.N1C(S)=NN=N1.Cl>C(Cl)Cl.CN(C)C=O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][C@@H:10]1[C:25](=[O:26])[N:12]2[C:13]([C:22]([O:24][Si:29]([CH3:32])([CH3:31])[CH3:30])=[O:23])=[C:14]([CH:39]([S:48][C:47]3[NH:46][N:45]=[N:44][N:43]=3)[CH3:40])[CH2:15][S:16][C@H:11]12)=[O:8]

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 6378Propylene OxideHCID 6397ChlorotrimethylsilaneHCID 85247Trimethylsilyl iodideHCID 23675321Cephalothin SodiumHCID 178482017HCID 178482017, compoundHCID 178527994HCID 178527994, compound

Product 1

HCID 178477399HCID 178477399, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 0.836 g (2 mmole) of sodium 7β-(2-thienylacetamido)-3-acetoxymethyl-3-cephem-4-carboxylate (sodium cephalothin) in 40 ml of dry methylene chloride maintained at the reflux temperature under a nitrogen atmosphere were added 0.7 ml (5.5 mmole) of chlorotrimethylsilane. The silylation of the C4 carboxy group was allowed to proceed 18 hours and the resulting yellow suspension was cooled to room temperature. The suspension was then reduced in volume by one-half under reduced pressure and 0.56 ml (4 mmole) of trimethylsilyl iodide were added rapidly. The color of the suspension gradually changed to a deep orange over one hour at room temperature. After 1.5 hours, 3 ml of dry dimethylformamide and 1 ml of propylene oxide were added to the orange suspension followed by 0.4 g (3.4 mmole) of 1-methyltetrazole-5-thiol. The reaction of the tetrazole thiol with the 3-iodomethyl derivative was allowed to proceed at room temperature for one hour after which 20 ml of methylene chloride and 20 ml of cold dilute hydrochloric acid (pH2) were added to the black reaction solution. The mixture was stirred vigorously for 20 minutes, was filtered and the organic layer separated. The organic layer was washed repeatedly with cold brine, dried over sodium sulfate and was filtered. Concentration of the organic layer afforded trimethylsilyl 7β-(2-thienylacetamido)-3-(1-methyl-1H-tetrazole-5-ylthiomethyl)-3-cephem-4-carboxylate contaminated with some DMF and 2-iodo-1-trimethylsilylpropanol.

Workup

  1. temperaturemaintained at the reflux temperature under a nitrogen atmosphere
  2. additionwere added rapidly
  3. customdeep orange over one hour
  4. customat room temperature
  5. waitAfter 1.5 hours
  6. waitto proceed at room temperature for one hour
  7. filtrationwas filtered
  8. customthe organic layer separated
  9. washThe organic layer was washed repeatedly with cold brine
  10. dry with materialdried over sodium sulfate
  11. filtrationwas filtered

Sources & evidence

ORD record
ord-f88e82074e1f4465b5ab9efefcc7a599
Source dataset
uspto-grants-1981_05
Patent number
US04266049

Reaction notes

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