Sodium Chloride → 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(3-methylureido)thiazol-4-yl]acetamido-3-cephem-4-carboxylic acid

HRID 127096Notes

Reaction equation

HRID 127096 reaction equation
[CH3:1][NH:2][C:3](=[O:14])[NH:4][C:5]1[S:6][CH:7]=[C:8]([CH2:10][C:11]([OH:13])=O)[N:9]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:21][N:22]1[C:26]([S:27][CH2:28][C:29]2[CH2:30][S:31][C@@H:32]3[CH:39]([NH2:40])[C:38](=[O:41])[N:33]3[C:34]=2[C:35]([OH:37])=[O:36])=[N:25][N:24]=[N:23]1.C[Si](CC(N)=O)(C)C.[Cl-].[Na+]>C(Cl)Cl.C(OCC)(=O)C>[CH3:21][N:22]1[C:26]([S:27][CH2:28][C:29]2[CH2:30][S:31][C@@H:32]3[CH:39]([NH:40][C:11](=[O:13])[CH2:10][C:8]4[N:9]=[C:5]([NH:4][C:3]([NH:2][CH3:1])=[O:14])[S:6][CH:7]=4)[C:38](=[O:41])[N:33]3[C:34]=2[C:35]([OH:37])=[O:36])=[N:25][N:24]=[N:23]1

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 24819Phosphorus pentachlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 20288645{2-[(Methylcarbamoyl)amino]-1,3-thiazol-4-yl}acetic acid

Product 1

HCID 887683043-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(3-methylureido)thiazol-4-yl]acetamido-3-cephem-4-carboxylic acidYield 40.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
-20 °C

Procedure

To a mixture of 2-(3-methylureido)thiazol-4-ylacetic acid (3.23 g.) in dried methylene chloride (50 ml.) was dropwise added a solution of phosphorus pentachloride in dried methylene chloride (80 ml.) with stirring under ice-cooling, and the mixture was stirred for 3 hours under ice-cooling. The precipitates were collected by filtration and washed with n-hexane. Thus obtained precipitates were added to a solution which was prepared by stirring a mixture of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (4.95 g.) and trimethylsilylacetamide (11.8 g.) in dried ethyl acetate (75 ml.) for 10 minutes at 40° C. and then by cooling it to at -20° C. The mixture was stirred for 1 hour at -20° to -10° C. and further stirred for 1 hour at -10° to 0° C. The mixture was cooled to at -20° C., and 10% aqueous solution of sodium chloride (7 ml.) was added therto, and then the mixture stirred for 10 minutes at room temperature. After the reaction, ethyl acetate layer was separated out, and the remaining precipitates were washed with ethyl acetate (50 ml.). To the precipitates was added water (30 ml.) and adjusted to pH 5 to 6 with sodium bicarbonate powder with stirring under ice-cooling. Thus obtained solution was subjected to alumina column chromatography, and the eluate was adjusted pH 2 with 17.5% hydrochloric acid. The precipitates were collected by filtration and dried over phosphorus pentachloride under reduced pressure to give white powder of 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(3-methylureido)thiazol-4-yl]acetamido-3-cephem-4-carboxylic acid (3.20 g.)

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 3 hours under ice-
  3. temperaturecooling
  4. filtrationThe precipitates were collected by filtration
  5. washwashed with n-hexane
  6. customThus obtained
  7. customprecipitates
  8. additionwere added to a solution which
  9. customwas prepared
  10. stirringby stirring
  11. stirringThe mixture was stirred for 1 hour at -20° to -10° C.
  12. stirringfurther stirred for 1 hour at -10° to 0° C
  13. additionwas added therto, and then the mixture
  14. stirringstirred for 10 minutes at room temperature
  15. customwas separated out
  16. customthe remaining precipitates
  17. washwere washed with ethyl acetate (50 ml.)
  18. additionTo the precipitates was added water (30 ml.)
  19. stirringwith stirring under ice-
  20. temperaturecooling
  21. filtrationThe precipitates were collected by filtration
  22. dry with materialdried over phosphorus pentachloride under reduced pressure

Sources & evidence

ORD record
ord-37d2c0c592b44250adbdc2229bf5bcf8
Source dataset
uspto-grants-1981_03
Patent number
US04254260

Reaction notes

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