N,N'-Dicyclohexylurea → 2-(2-Tritylamino-4-thiazolyl)-2-hydroxyimino-acetic acid

HRID 1758716Notes

Reaction equation

HRID 1758716 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[C:16]([NH:35][C:36]1[S:37][CH:38]=[C:39]([C:41](=[N:45][O:46]C(C)(OC)C)[C:42]([OH:44])=[O:43])[N:40]=1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(NC1CCCCC1)(NC1CCCCC1)=O.CC1SC(SCC2CS[C@@H]3C(N)C(=O)N3C=2C(O)=O)=NN=1>[N+](C)([O-])=O.C(N(CC)CC)C.C(Cl)Cl>[C:16]([NH:35][C:36]1[S:37][CH:38]=[C:39]([C:41](=[N:45][OH:46])[C:42]([OH:44])=[O:43])[N:40]=1)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 4277N,N'-DicyclohexylureaHCID 10868DicyclohexylcarbodiimideHCID 129420347-Amino-3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acidHCID 536416812-(2-Tritylamino-4-thiazolyl)-2-(1-methyl-1-methoxyethoxyimino)-acetic acid

Product 1

HCID 730781342-(2-Tritylamino-4-thiazolyl)-2-hydroxyimino-acetic acid

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6375NitromethaneSolventHCID 8471TriethylamineSolvent

Procedure

0.23 g of dicyclohexylcarbodiimide were added under argon at 20° C. to a mixture of 1.002 g of the syn isomer of 2-(2-tritylamino-4-thiazolyl)-2-(1-methyl-1-methoxy-ethoxyimino)-acetic acid and 3 ml of methylene chloride and the mixture was stirred at 20°-25° C. for one hour to obtain a suspension of dicyclohexylurea. In a second flask, 0.28 ml of triethylamine were added at 20° to 25° C. to a suspension of 0.344 g of 3-[(5-methyl-1,3,4-thiadiazol-2-yl)-thiomethyl]-7-amino-ceph-3-eme-4-carboxylic acid in 2 ml of nitromethane to form a brown solution which was added over 5 minutes with stirring at 20°-25° C. to the first suspension. The mixture was rinsed with methylene chloride and was then stirred for 2 hours and was vacuum filtered to remove dicyclohexylurea (0.2 g). The filter was rinsed with methylene chloride and the filtrate and 8 ml of N hydrochloric acid were stirred. The mixture was vacuum filtered and the brown product was rinsed with water and methylene chloride to obtain 0.4 g of mainly the starting product. The filtrate was washed with distilled water until the wash water was neutral, dried and distilled to dryness under reduced pressure. The residue was added to 5 ml of ethyl acetate and the mixture was vacuum filtered at room temperature. The product was rinsed with ethyl acetate to obtain 0.32 g of the syn isomer of 2-(2-tritylamino-4-thiazolyl)-2-hydroxyimino-acetic acid.

Workup

  1. customto obtain
  2. customto form a brown solution which
  3. additionwas added over 5 minutes
  4. stirringwith stirring at 20°-25° C. to the first suspension
  5. washThe mixture was rinsed with methylene chloride
  6. stirringwas then stirred for 2 hours
  7. filtrationfiltered
  8. customto remove dicyclohexylurea (0.2 g)
  9. washThe filter was rinsed with methylene chloride
  10. stirringthe filtrate and 8 ml of N hydrochloric acid were stirred
  11. filtrationfiltered
  12. washthe brown product was rinsed with water and methylene chloride
  13. customto obtain 0.4 g of mainly the starting product
  14. washThe filtrate was washed with distilled water until the wash water
  15. customdried
  16. distillationdistilled to dryness under reduced pressure
  17. additionThe residue was added to 5 ml of ethyl acetate
  18. filtrationfiltered at room temperature
  19. washThe product was rinsed with ethyl acetate

Sources & evidence

ORD record
ord-0c9d3f24aec944a5843cfe9c9359017b
Source dataset
uspto-grants-1983_02
Patent number
US04374834

Reaction notes

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