Hydrochloric Acid → HCID 178433977, compound

HRID 1858519Notes

Reaction equation

HRID 1858519 reaction equation
P(Cl)(Cl)(Cl)=O.[C:6]([O:10][C:11]([NH:13][C:14]1[S:18][N:17]=[C:16]([CH2:19][C:20]([OH:22])=O)[N:15]=1)=[O:12])([CH3:9])([CH3:8])[CH3:7].[NH2:23][C@@H:24]1[C:40](=[O:41])[N:26]2[C:27]([C:37]([OH:39])=[S:38])=[C:28]([C:31]3[S:32][C:33]([CH3:36])=[N:34][N:35]=3)[CH2:29][S:30][C@H:25]12.C[Si](C)(C)NC(=O)C.C(=O)([O-])O.[Na+].Cl>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[C:6]([O:10][C:11]([NH:13][C:14]1[S:18][N:17]=[C:16]([CH2:19][C:20]([NH:23][C@@H:24]2[C:40](=[O:41])[N:26]3[C:27]([C:37]([OH:39])=[S:38])=[C:28]([C:31]4[S:32][C:33]([CH3:36])=[N:34][N:35]=4)[CH2:29][S:30][C@H:25]23)=[O:22])[N:15]=1)=[O:12])([CH3:7])([CH3:8])[CH3:9]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 25989Acetamide, N-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 2212437678093-06-8HCID 178433972HCID 178433972, compound

Product 1

HCID 178433977HCID 178433977, compoundYield 57.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent3×

Procedure

Phosphorus oxychloride (473 μl) was added dropwise to a mixture of N,N-dimethylformamide (388 μl) and ethyl acetate (1 ml) under ice-cooling. After being stirred for 10 minutes at the same temperature, the mixture was cooled until a precipitate appeared. To the suspension was added tetrahydrofuran (17 ml). The suspension was stirred at the same temperature for 30 minutes. To the suspension was added 2-(5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetic acid (1.0 g). The mixture was stirred at the same temperature for 30 minutes to give an activated acid solution. On the other hand, to a suspension of 7β-amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thio-3-cephem-4-carboxylic acid (1.16 g) in tetrahydrofuran (17 ml) was added N-trimethylsilylacetamide (3.7 g). The suspension was stirred at 20-40° C. for 40 minutes to give a clear solution. To the solution was added the activated acid solution prepared above at -20° C. The mixture was stirred at -20~5° C. for 40 minutes. The reaction mixture was added to a mixture of ethyl acetate (100 ml), sodium hydrogen carbonate (1.59 g) and water (100 ml). To the separated aqueous solution was added ethyl acetate (100 ml). The mixture was adjusted to pH 2 with 1N-hydrochloric acid. The organic layer was washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diethyl ether to give 7β-[2-(5-tert-butoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetamido]-3-(5-methyl-1,3,4-thiadiazol-2-yl)thio-3-cephem-4-carboxylic acid (1.17 g).

Workup

  1. temperaturecooling
  2. temperaturethe mixture was cooled until a precipitate
  3. stirringThe suspension was stirred at the same temperature for 30 minutes
  4. stirringThe mixture was stirred at the same temperature for 30 minutes
  5. customto give an activated acid solution
  6. stirringThe suspension was stirred at 20-40° C. for 40 minutes
  7. customto give a clear solution
  8. additionTo the solution was added the activated acid solution
  9. customprepared above at -20° C
  10. stirringThe mixture was stirred at -20~5° C. for 40 minutes
  11. washThe organic layer was washed with saturated aqueous sodium chloride
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-c9efafa7731644a9a08f787521be3464
Source dataset
uspto-grants-2000_11
Patent number
US06150351

Reaction notes

Loading…