Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate

HRID 364534Notes

Reaction equation

HRID 364534 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[NH2:21][CH:22]1[C:43](=[O:44])[N:24]2[C:25]([C:30]([O:32][CH2:33][C:34]3[CH:39]=[CH:38][C:37]([N+:40]([O-:42])=[O:41])=[CH:36][CH:35]=3)=[O:31])=[C:26]([OH:29])[CH2:27][S:28][C@H:23]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[N:18][O:19][CH3:20])[C:15]([NH:21][CH:22]2[C:43](=[O:44])[N:24]3[C:25]([C:30]([O:32][CH2:33][C:34]4[CH:35]=[CH:36][C:37]([N+:40]([O-:42])=[O:41])=[CH:38][CH:39]=4)=[O:31])=[C:26]([OH:29])[CH2:27][S:28][C@H:23]23)=[O:17])[N:13]=1)=[O:7]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 27245112-(2-Formylamino-1,3-Thiazol-4-Yl)-2-(Methoxyimino)Acetic AcidHCID 11708267BistrimethylsilylacetamidHCID 681232354-Nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate

Product 1

HCID 1317124524-Nitrobenzyl 7-[2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylateYield 43.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Phosphoryl chloride (2.87 g.) was dropwise added to a solution of N,N-dimethylformamide (1.37 g.) in ethyl acetate (10 ml.) at 5° to 10° C. Ethyl acetate (40 ml.) was added to the solution, and stirred under ice cooling for 40 minutes. To the solution was added 2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetic acid (syn isomer, 3.58 g.), and the solution was stirred at 0° to 5° C. for 40 minutes. The resultant solution was added all at once to a mixture of 4-nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate (5 g.), ethyl acetate (50 ml.), trimethylsilylacetamide (14.3 g.) and bis(trimethylsilyl)acetamide (5.8 g.) at -15° C., and stirred at -20° to -15° C. for 1.2 hours. Water (50 ml.) was added to the resultant solution at -25° to -20° C., and stirred until the temperature rise 5° C. The aqueous layer was separated and extracted with ethyl acetate. The ethyl acetate layer and extract were combined, washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After the solution was concentrated to a volume of 50 ml. under reduced pressure, the precipitates were collected by filtration and washed with ethyl acetate to give 4-nitrobenzyl 7-[2-(2-formamido-4-thiazolyl)-2-methoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate (syn isomer, 3.5 g.), mp 163° C. (dec.).

Workup

  1. stirringthe solution was stirred at 0° to 5° C. for 40 minutes
  2. stirringstirred at -20° to -15° C. for 1.2 hours
  3. stirringstirred until the temperature
  4. customrise 5° C
  5. customThe aqueous layer was separated
  6. extractionextracted with ethyl acetate
  7. extractionThe ethyl acetate layer and extract
  8. washwashed with a saturated aqueous solution of sodium chloride
  9. dry with materialdried over magnesium sulfate
  10. concentrationAfter the solution was concentrated to a volume of 50 ml
  11. filtrationunder reduced pressure, the precipitates were collected by filtration
  12. washwashed with ethyl acetate

Sources & evidence

ORD record
ord-65158f56c8fb42afa80458e0247c4d2c
Source dataset
uspto-grants-1986_08
Patent number
US04604456

Reaction notes

Loading…