Phosphorus oxychloride → 7-[2-(2-Aminothiazol-4-yl)-2-allyloxyiminoacetamido]-3-cephem-4-carboxylic acid

HRID 1650512Notes

Reaction equation

HRID 1650512 reaction equation
P(Cl)(Cl)(Cl)=O.[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH2:18][CH:19]=[CH2:20])[C:13]([OH:15])=O)[N:11]=1.C[Si](CC(N)=O)(C)C.[NH2:29][CH:30]1[C:40](=[O:41])[N:32]2[C:33]([C:37]([OH:39])=[O:38])=[CH:34][CH2:35][S:36][C@H:31]12.C(=O)(O)[O-].[Na+]>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[NH2:6][C:7]1[S:8][CH:9]=[C:10]([C:12](=[N:16][O:17][CH2:18][CH:19]=[CH2:20])[C:13]([NH:29][CH:30]2[C:40](=[O:41])[N:32]3[C:33]([C:37]([OH:39])=[O:38])=[CH:34][CH2:35][S:36][C@H:31]23)=[O:15])[N:11]=1

Participants

10

Reactant 5

HCID 24813Phosphorus oxychloride2×HCID 357676Acetamide, 2-(trimethylsilyl)-2×HCID 516892Sodium BicarbonateHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 544842532-(2-Aminothiazol-4-yl)-2-allyloxyiminoacetic acid

Product 1

HCID 1317124657-[2-(2-Aminothiazol-4-yl)-2-allyloxyiminoacetamido]-3-cephem-4-carboxylic acidYield 44.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Phosphoryl chloride (0.84 g.) was added dropwise to a stirred suspension of 2-(2-aminothiazol-4-yl)-2-allyloxyiminoacetic acid (syn isomer, 1.0 g.), tetrahydrofuran (10 ml.) and water (0.05 ml.) at 5° C., and stirred at the same temperature for 20 minutes. Trimethylsilylacetamide (0.66 g.), phosphoryl chloride (0.84 g.) and N,N-dimethylformamide (0.45 g.) were added to a solution, and stirred at 5° C. for an hour to prepare the activated acid solution. On the other hand, trimethylsilylacetamide (4.0 g.) was added to a suspension of 7-amino-3-cephem-4-carboxylic acid (0.88 g.) in tetrahydrofuran (10 ml.) at 40° C., and stirred for 30 minutes. To the solution was added all at once the activated acid solution obtained above at -20° C., and stirred at 0° C. for an hour. After water (20 ml.) was added to the resultant solution at -20° C., the solution was adjusted to pH 7.5 with an aqueous solution of sodium bicarbonate. Ethyl acetate was added to the solution, and the aqueous layer was separated. The solution was washed with ethyl acetate and diisopropyl ether in turn, adjusted to pH 5.0 and treated with activated charcoal. After the solution was adjusted to pH 3.0, the precipitates were collected by filtration, washed with water and dried over phosphorus pentoxide to give 7-[2-(2-aminothiazol-4-yl)-2-allyloxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer, 0.8 g.).

Workup

  1. stirringstirred at 5° C. for an hour
  2. customto prepare the activated acid solution
  3. stirringstirred for 30 minutes
  4. additionTo the solution was added all at once the activated acid solution
  5. customobtained above at -20° C.
  6. stirringstirred at 0° C. for an hour
  7. customthe aqueous layer was separated
  8. washThe solution was washed with ethyl acetate and diisopropyl ether in turn
  9. additiontreated with activated charcoal
  10. filtrationthe precipitates were collected by filtration
  11. washwashed with water
  12. dry with materialdried over phosphorus pentoxide

Sources & evidence

ORD record
ord-2c42f6754c664bfc96f6bc36d1ad4928
Source dataset
uspto-grants-1990_05
Patent number
US04923998

Reaction notes

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