Water → 3-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid

HRID 2198537Notes

Reaction equation

HRID 2198537 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.N[CH:17]1[C:35](=[O:36])[N:19]2[C:20]([C:32]([OH:34])=[O:33])=[C:21]([CH2:24][S:25][C:26]3[N:30]([CH3:31])[N:29]=[N:28][N:27]=3)[CH2:22][S:23][C@H:18]12.O>C1COCC1.CC#N.CN(C=O)C>[CH3:31][N:30]1[C:26]([S:25][CH2:24][C:21]2[CH2:22][S:23][C@@H:18]3[CH2:17][C:35](=[O:36])[N:19]3[C:20]=2[C:32]([OH:34])=[O:33])=[N:27][N:28]=[N:29]1

Participants

7

Reactant 3

HCID 962WaterHCID 10868DicyclohexylcarbodiimideHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacid

Product 1

HCID 1186430063-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

To a solution of 2-[2-(N-chloroacetyl)-imino-3-methoxy-4-thiazolinyl]-2-methoxyimino-acetic acid (3.07 g) in anhydrous THF (120 ml) cooled at -5° C., N,N'-dicyclohexylcarbodiimide (2.06 g) was added. After stirring for 10 minutes at -5° C. and 50 minutes at room temperature, the precipitate dicyclohexylurea was filtered off, and the solution was added into a cooled (-10° C.) solution obtained by stirring 7-amino-3-[(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid (3.3 g) and N,O-bis-(trimethyl-silyl)-acetamide (8.1 g) in anhydrous THF (200 ml), CH3CN (80 ml) and DMF (4 ml) for 1 hour at 50° C. The mixture was stirred 20 minutes at -10° C. and 90 minutes at room temperature. H2O (10 ml) was added in order to hydrolize the silylated product, and the major part of the solvents were evaporated under reduced pressure. The residue was partitioned between H2O (50 ml) and ethyl acetate (100 ml); the organic layer was separated and the aqueous one was extracted again with ethyl acetate. The combined extracts were dried (Na2SO4), concentrated to a small volume and diluted with ethyl ether. The precipitated solid was collected and washed with ethyl ether, thus giving 5.1 g of 7β[2-(2-N-chloroacetyl)-imino-3-methoxy-4-thiazolinyl]-2-methoxyimino-acetamido]-3-[(1-methyl-1,2,3,4-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid. This compound was dissolved in MeCN (200 ml) and heated with diphenyldiazomethane (1.9 g). After stirring 1 hour at room temperature, the solvent was evaporated, the residue was taken up with ethyl acetate, washed with dilute NaHCO3 solution, then with water, dried (Na2SO4), and again evaporated to dryness. The residue was triturated with ethyl ether and filtered, thus affording 6.3 g of benzhydryl ester.

Workup

  1. filtrationthe precipitate dicyclohexylurea was filtered off
  2. additionthe solution was added into
  3. temperaturea cooled (-10° C.) solution
  4. customobtained
  5. stirringThe mixture was stirred 20 minutes at -10° C. and 90 minutes at room temperature
  6. customthe major part of the solvents were evaporated under reduced pressure
  7. customThe residue was partitioned between H2O (50 ml) and ethyl acetate (100 ml)
  8. customthe organic layer was separated
  9. extractionthe aqueous one was extracted again with ethyl acetate
  10. dry with materialThe combined extracts were dried (Na2SO4)
  11. concentrationconcentrated to a small volume
  12. additiondiluted with ethyl ether
  13. customThe precipitated solid was collected
  14. washwashed with ethyl ether

Sources & evidence

ORD record
ord-90337ea2dabb46b6afc88145a163f4a0
Source dataset
uspto-grants-1982_11
Patent number
US04358448

Reaction notes

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