Triethylamine → 7beta-phenylacetamido-3-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid

HRID 28017

Reaction equation

HRID 28017 reaction equation
C(N(CC)CC)C.[C:8]1([CH2:14][C:15]([NH:17][C@@H:18]2[C:30](=[O:31])[N:20]3[C:21]([C:27]([OH:29])=[O:28])=[C:22]([CH2:25]O)[CH2:23][S:24][C@H:19]23)=[O:16])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.[SH:39][C:40]1[N:44]([CH3:45])[N:43]=[N:42][N:41]=1.CNC(N1C2C(=CC=CC=2)C(=O)C1=O)=O>C(#N)C>[C:8]1([CH2:14][C:15]([NH:17][C@@H:18]2[C:30](=[O:31])[N:20]3[C:21]([C:27]([OH:29])=[O:28])=[C:22]([CH2:25][S:39][C:40]4[N:44]([CH3:45])[N:43]=[N:42][N:41]=4)[CH2:23][S:24][C@H:19]23)=[O:16])[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2835543N-(methylcarbamoyl)isatinHCID 705426117beta-Phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylic acid triethylamine saltHCID 178482017HCID 178482017, compound

Product 1

HCID 133441437beta-phenylacetamido-3-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
30 °C

Procedure

In acetonitrile (14 ml) is dissolved 7β-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylic acid triethylamine salt (900 mg), followed by the addition of triethylamine (200 mg), 5-mercapto-1-methyl-1H-tetrazole (464 mg) and N-(methylcarbamoyl)isatin (916 mg). The mixture is stirred at 30° C. overnight. The solvent is then distilled off and the residue is dissolved by the addition of water and ethyl acetate. After separation, the water layer is taken, rinsed once with ethyl acetate and rendered acidic with hydrochloric acid. Following the addition of ethyl acetate, the mixture is stirred for 30 minutes. After separation , the organic layer is taken and rinsed with an aqueous solution of sodium chloride. It is extracted with an aqueous solution of sodium hdyrogen carbonate. The water layer is purified by column chromatography on Sephadex LH-20 . The fractions rich in the contemplated compound are pooled, concentrated, rendered acidic with phosphoric acid and extracted with ethyl acetate. After drying, the extract is concentrated, followed by addition of ether to the residue. The procedure provides 7β-phenylacetamido-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid. The NMR spectrum of this product is in good agreement with that of the compound obtained in Example 6.

Workup

  1. distillationThe solvent is then distilled off
  2. dissolutionthe residue is dissolved by the addition of water and ethyl acetate
  3. customAfter separation
  4. washrinsed once with ethyl acetate
  5. additionthe addition of ethyl acetate
  6. stirringthe mixture is stirred for 30 minutes
  7. customAfter separation
  8. washrinsed with an aqueous solution of sodium chloride
  9. extractionIt is extracted with an aqueous solution of sodium hdyrogen carbonate
  10. customThe water layer is purified by column chromatography on Sephadex LH-20
  11. concentrationconcentrated
  12. extractionextracted with ethyl acetate
  13. customAfter drying
  14. concentrationthe extract is concentrated
  15. additionfollowed by addition of ether to the residue

Sources & evidence

ORD record
ord-8f8cd337db484f859333750ec22af914
Source dataset
uspto-grants-1980_09
Patent number
US04224441

Linked notes

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