N,N-Dimethylaniline → 7-Aminocephalosporanic acid

HRID 1863239Notes

Reaction equation

HRID 1863239 reaction equation
[Na].C1(C)C=CC(S(N)(=O)=O)=CC=1.[CH3:13][C:14]([O:16][CH2:17][C:18]1[CH2:37][S:36][C@@H:21]2[C@H:22]([NH:25]C(CCC[C@@H](N)C(O)=O)=O)[C:23](=[O:24])[N:20]2[C:19]=1[C:38]([OH:40])=[O:39])=[O:15].CN(C)C1C=CC=CC=1.C[Si](C)(Cl)Cl.P(Cl)(Cl)(Cl)(Cl)Cl>C(Cl)Cl.CO.O.C(N(CC)CC)C>[CH3:13][C:14]([O:16][CH2:17][C:18]1[CH2:37][S:36][C@@H:21]2[C@H:22]([NH2:25])[C:23](=[O:24])[N:20]2[C:19]=1[C:38]([OH:40])=[O:39])=[O:15]

Participants

11

Reactant 6

HCID 949N,N-Dimethylaniline3×HCID 6269P-ToluenesulfonamideHCID 6398DichlorodimethylsilaneHCID 24819Phosphorus pentachlorideHCID 65536Cephalosporin CHCID 5360545Sodium

Product 1

HCID 4413287-Aminocephalosporanic acidYield 65%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
28 °C

Procedure

3.07 g of the sodium salt of toluene-p-sulphonamide of cephalosporin C having a titre of 83.8% were suspended in 30 ml of methylene chloride. 1.4 ml of triethylamine and 1.9 ml of N,N-dimethylaniline were then added and then 2.4 ml of dimethyldichlorosilane were added over 5 minutes with stirring. Stirring was maintained for 1 hour at 28° C. The solution was then cooled to a temperature of -60° C., after which a solution of 3.13 g of PCl5 in 30 ml of methylene chloride was slowly added, followed by 2.5 ml of N,N-dimethylaniline. After 2 hours of agitation at -40° C. the temperature was reduced again to -60° C. and 0.34 of N,N-dimethylaniline in 9 ml of methanol were added. After two hours at -40° C., 10 ml of water at 90° C. were added and agitation was continued for 5 minutes at 4° C. The aqueous phase was then recovered and the organic phase was extracted with 10 ml of cool water. The combined aqueous extracts were washed with 10 ml of methylene chloride and the pH was adjusted to 3.6-3.7 by addition of concentrated aqueous ammonia solution, with stirring. After allowing the mixture to rest overnight at a low temperature, the precipitate which formed was filtered, washed with methylene chloride, water, acetone and ether, to give 0.80 g (65%) of 7-aminocephalosporanic acid with a spectrophotometric titre of 94.4%.

Workup

  1. stirringStirring
  2. temperatureThe solution was then cooled to a temperature of -60° C.
  3. waitAfter two hours at -40° C.
  4. waitagitation was continued for 5 minutes at 4° C
  5. customThe aqueous phase was then recovered
  6. extractionthe organic phase was extracted with 10 ml of cool water
  7. washThe combined aqueous extracts were washed with 10 ml of methylene chloride
  8. additionthe pH was adjusted to 3.6-3.7 by addition of concentrated aqueous ammonia solution
  9. stirringwith stirring
  10. waitto rest overnight at a low temperature
  11. customthe precipitate which formed
  12. filtrationwas filtered
  13. washwashed with methylene chloride, water, acetone and ether

Sources & evidence

ORD record
ord-c249e06731d24a1c8fa4a89032123a0c
Source dataset
uspto-grants-1979_09
Patent number
US04168375

Reaction notes

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