Phosphorus oxychloride → HCID 131712734, compound

HRID 1388481Notes

Reaction equation

HRID 1388481 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([OH:14])=O)([CH3:8])[CH3:7].[NH2:23][CH:24]1[C:42](=[O:43])[N:26]2[C:27]([C:39]([OH:41])=[O:40])=[C:28]([CH2:31][S:32][C:33]3[N:37]([CH3:38])[N:36]=[N:35][N:34]=3)[CH2:29][S:30][C@H:25]12.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.O.CC(C)=O.CN(C)C=O>[CH:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([NH:23][CH:24]1[C:42](=[O:43])[N:26]2[C:27]([C:39]([OH:41])=[O:40])=[C:28]([CH2:31][S:32][C:33]3[N:37]([CH3:38])[N:36]=[N:35][N:34]=3)[CH2:29][S:30][C@H:25]12)=[O:14])([CH3:7])[CH3:8]

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 130208137-Amino-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylicacidHCID 538092752-(2-Formamidothiazol-4-yl)-2-isopropoxyiminoacetic acid

Product 1

HCID 131712734HCID 131712734, compoundYield 60%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Phosphorus oxychloride (0.92 g) was added dropwise over 3 minutes at -5° to -10° C. to a solution of dimethylformamide (0.44 g) in ethyl acetate (2 ml). Ethyl acetate (20 ml) was added thereto and after 10 minutes, 2-isopropoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetic acid (syn isomer)(1.29 g) was added thereto at -5° to -10° C. The mixture was stirred for 10 minutes to give a clear solution. On the other hand, 7-amino-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.64 g) was dissolved under stirring in a solution of sodium bicarbonate (1.68 g) in water (30 ml), and then acetone (20 ml) was added thereto. To the solution was added dropwise with stirring the ethyl acetate solution obtained above at 0° to 5° C. and at pH 6.5 to 7.5. After stirring for 20 minutes at the same temperature, the aqueous layer was separated and acetone was distilled off. The remaining aqueous layer was adjusted to pH 3.0 with 10% hydrochloric acid under ice-cooling and stirring. Precipitates were collected by filtration, washed with water and dried to give 7-[2-isopropoxyimino-2-(2-formamido-1,3-thiazol-4-yl)acetamido]-3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.7 g).

Workup

  1. customat -5° to -10° C
  2. customto give a clear solution
  3. additionTo the solution was added dropwise
  4. customobtained above at 0° to 5° C. and at pH 6.5 to 7.5
  5. stirringAfter stirring for 20 minutes at the same temperature
  6. customthe aqueous layer was separated
  7. distillationacetone was distilled off
  8. temperaturecooling
  9. stirringstirring
  10. customPrecipitates
  11. filtrationwere collected by filtration
  12. washwashed with water
  13. customdried

Sources & evidence

ORD record
ord-7bac9d90890242909c7c60e8a1cc030c
Source dataset
uspto-grants-1984_02
Patent number
US04431643

Reaction notes

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