Formamide → (6R,7R)-7-Amino-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid

HRID 2292390Notes

Reaction equation

HRID 2292390 reaction equation
[NH2:1][C@@H:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH2:9]O)[CH2:7][S:8][C@H:3]12.[SH:16][C:17]1[N:21]([CH3:22])[N:20]=[N:19][N:18]=1.C(N)=O.P1(OC2C=CC=CC=2O1)(OC)=O.N.O>C(Cl)Cl.C(#N)C.C(N(CC)CC)C>[NH2:1][C@@H:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH2:9][S:16][C:17]3[N:21]([CH3:22])[N:20]=[N:19][N:18]=3)[CH2:7][S:8][C@H:3]12

Participants

9

Reactant 5

HCID 713FormamideHCID 11031679(6R-trans)-7-Amino-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 12617050Methyl o-phenylene phosphateHCID 12896473Azane;hydrateHCID 178482017HCID 178482017, compound

Product 1

HCID 483175(6R,7R)-7-Amino-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidYield 85.4%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolvent2×HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To the mixture of 230 mg of 7β-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid, 174 mg of 5-mercapto-1-methyl-1H-tetrazole, 4 ml of formamide and 1 ml of acetonitrile was added 253 mg of triethylamine under stirring and cooling with ice bath. To the resulting solution were added a solution of 650 mg of methyl o-phenylene phosphate in 2 ml of methylene chloride and 5 ml of acetonitrile under stirring and cooling at -10° C. to 0° C., followed by stirring for 0.5 hour at 0° C. to 5° C. The resulting precipitate was collected by filtration, washed with 5 ml of acetonitrile and suspended in a mixed solution of 6 ml of water and 2 ml of acetonitrile. To this suspension was added about 0.1 ml of 35% hydrochloric acid to obtain a clear solution. After adjusting the pH of the solution to 4 by addition of 25% ammonia-water under cooling with ice bath, the resulting crystals were collected by filtration, washed with 2 ml of cold water and dried in vacuo to give 280 mg (yield 85.3%) of 7β-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid.

Workup

  1. temperaturecooling with ice bath
  2. stirringunder stirring
  3. temperaturecooling at -10° C. to 0° C.
  4. stirringby stirring for 0.5 hour at 0° C. to 5° C
  5. filtrationThe resulting precipitate was collected by filtration
  6. washwashed with 5 ml of acetonitrile
  7. additionTo this suspension was added about 0.1 ml of 35% hydrochloric acid
  8. customto obtain a clear solution
  9. temperatureunder cooling with ice bath
  10. filtrationthe resulting crystals were collected by filtration
  11. washwashed with 2 ml of cold water
  12. customdried in vacuo

Sources & evidence

ORD record
ord-01c3f7389bb740b4ab2148d3c4bc143b
Source dataset
uspto-grants-1989_01
Patent number
US04801703

Reaction notes

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