Dimethylformamide → HCID 131711625, compound

HRID 1382074Notes

Reaction equation

HRID 1382074 reaction equation
CN(C)C=O.P(Cl)(Cl)(Cl)=O.[CH3:11][O:12][N:13]=[C:14]([C:18]1[N:19]([CH3:28])[C:20](=[N:23][S:24]([CH3:27])(=[O:26])=[O:25])[S:21][CH:22]=1)[C:15]([OH:17])=O.[NH2:29][CH:30]1[C:48](=[O:49])[N:32]2[C:33]([C:45]([OH:47])=[O:46])=[C:34]([CH2:37][S:38][C:39]3[N:43]([CH3:44])[N:42]=[N:41][N:40]=3)[CH2:35][S:36][C@H:31]12>C(Cl)Cl.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>[CH3:11][O:12][N:13]=[C:14]([C:18]1[N:19]([CH3:28])[C:20](=[N:23][S:24]([CH3:27])(=[O:26])=[O:25])[S:21][CH:22]=1)[C:15]([NH:29][CH:30]1[C:48](=[O:49])[N:32]2[C:33]([C:45]([OH:47])=[O:46])=[C:34]([CH2:37][S:38][C:39]3[N:43]([CH3:44])[N:42]=[N:41][N:40]=3)[CH2:35][S:36][C@H:31]12)=[O:17]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 88495332HCID 88495332, compound

Product 1

HCID 131711625HCID 131711625, compoundYield 66.6%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 11708267BistrimethylsilylacetamidSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of dimethylformamide (0.22 g.) and phosphorus oxychloride (0.46 g.) was warmed for 1 hour at 40° C. The mixture was dissolved in dry methylene chloride (20 ml.) and 2-methoxyimino-2-(2-mesylimino-3-methyl-2,3-dihydro-1,3-thiazol-4-yl)acetic acid (anti isomer) (0.73 g.) was added thereto with stirring and ice-cooling, after which the resulting mixture was stirred for 1.5 hours under ice-cooling. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (0.82 g.) was dissolved in a solution of bis(trimethylsilyl)acetamide (1.5 g.) in dry methylene chloride (20 ml.). To this solution was added at -30° C. the above obtained methylene chloride solution, after which the mixture was stirred for 2 hours at -5° to -20° C. After distilling off methylene chloride at low temperature, water was added to the residue and the mixture was extracted with ethyl acetate. The extract was washed with a sodium chloride aqueous solution and water (50 ml.) was added thereto. The resulting mixture was adjusted to pH 7 with an aqueous solution of sodium bicarbonate and the aqueous layer was separated. The aqueous layer was adjusted to pH 1.5, saturated with sodium chloride and extracted with ethyl acetate. The extract was washed with a sodium chloride aqueous solution and dried over magnesium sulfate. The solvent was distilled off and the residue was pulverized by a mixture of diisopropyl ether and ether. The powder was collected by filtration and dried to give 7-[2-methoxyimino-2-(2-mesylimino-3-methyl-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (anti isomer) (1.0 g.). This powder (1.0 g.) was suspended in water (30 ml.) and dissolved by adjusting to pH 6 by an aqueous solution of sodium bicarbonate. After removing the solvent by bubbling of nitrogen gas, the aqueous solution was lyophilized to give sodium 7-[2-methoxyimino-2-(2-mesylimino-3-methyl-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylate (anti isomer) (0.98 g.).

Workup

  1. temperatureice-cooling
  2. stirringafter which the resulting mixture was stirred for 1.5 hours under ice-
  3. temperaturecooling
  4. additionTo this solution was added at -30° C. the
  5. stirringafter which the mixture was stirred for 2 hours at -5° to -20° C
  6. distillationAfter distilling off methylene chloride at low temperature, water
  7. additionwas added to the residue
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with a sodium chloride aqueous solution and water (50 ml.)
  10. additionwas added
  11. customthe aqueous layer was separated
  12. extractionextracted with ethyl acetate
  13. washThe extract was washed with a sodium chloride aqueous solution
  14. dry with materialdried over magnesium sulfate
  15. distillationThe solvent was distilled off
  16. additionthe residue was pulverized by a mixture of diisopropyl ether and ether
  17. filtrationThe powder was collected by filtration
  18. customdried

Sources & evidence

ORD record
ord-2bce8f3b33b04b38b537126ab32e04bd
Source dataset
uspto-grants-1989_02
Patent number
US04804752

Reaction notes

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