Water → HCID 131711121, compound

HRID 839270Notes

Reaction equation

HRID 839270 reaction equation
C(N(CC)CC)C.C(Cl)(=O)C(C)(C)C.N[CH:16]1[C:34](=[O:35])[N:18]2[C:19]([C:31]([OH:33])=[O:32])=[C:20]([CH2:23][S:24][C:25]3[S:26][C:27]([CH3:30])=[N:28][N:29]=3)[CH2:21][S:22][C@H:17]12.O>CC(C)=O>[CH3:30][C:27]1[S:26][C:25]([S:24][CH2:23][C:20]2[CH2:21][S:22][C@@H:17]3[CH2:16][C:34](=[O:35])[N:18]3[C:19]=2[C:31]([OH:33])=[O:32])=[N:29][N:28]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 129420347-Amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 131711121HCID 131711121, compoundYield 114.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

3-(N-tert-butoxycarbonylamino)-3-(2-thienyl)-DL-propionic acid (10.8 g.) and triethylamine (4.04 g.) were dissolved in dry acetone (200 ml.) with stirring at room temperature. On cooling the solution at -10° to -15° C, pivaloyl chloride (4.82 g.) was added to the solution all at once with stirring. The mixture was stirred at -10° to -15° C for an hour and then cooled to -40° to -50° C. To the mixture was added a mixture of 7-amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (13.76 g.), triethylamine (12.0 g.), water (40 ml.) and acetone (160 ml.) all at once. The resultant mixture was stirred at -40° to -50° C for 1.5 hours and then at room temperature for 2 hours. The acetone was removed from the reaction mixture under reduced pressure and the residue was washed with ethyl acetate. The aqueous layer was separated, adjusted with 10% hydrochloric acid to pH 1 and extracted with ethyl acetate. The extract was washed with water and an aqueous solution of sodium chloride, dried over magnesium sulfate, treated with activated charcoal and then concentrated under reduced pressure. Ether was added to the concentrate and the mixture was stirred for 3 hours. The precipitate was filtered to give 7-[3-(N-tert-butoxycarbonylamino)-3-(2-thienyl)-DL-propionamido[-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (15.1 g.), m.p. 130° to 135° C (dec.).

Workup

  1. temperatureOn cooling the solution at -10° to -15° C
  2. stirringwith stirring
  3. stirringThe mixture was stirred at -10° to -15° C for an hour
  4. temperaturecooled to -40° to -50° C
  5. additionTo the mixture was added
  6. customThe acetone was removed from the reaction mixture under reduced pressure
  7. washthe residue was washed with ethyl acetate
  8. customThe aqueous layer was separated
  9. extractionextracted with ethyl acetate
  10. washThe extract was washed with water
  11. dry with materialan aqueous solution of sodium chloride, dried over magnesium sulfate
  12. additiontreated with activated charcoal
  13. concentrationconcentrated under reduced pressure
  14. additionEther was added to the
  15. concentrationconcentrate
  16. stirringthe mixture was stirred for 3 hours
  17. filtrationThe precipitate was filtered

Sources & evidence

ORD record
ord-cea9a1a0a5f94420bf414e6c340e4e28
Source dataset
uspto-grants-1978_06
Patent number
US04094872

Reaction notes

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