Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate

HRID 1075228Notes

Reaction equation

HRID 1075228 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[N:14]=[C:13]([C:15](=[N:19][O:20][CH3:21])[C:16]([OH:18])=O)[CH:12]=[CH:11][CH:10]=1)=[O:7].[NH2:22][CH:23]1[C:43](=[O:44])[N:25]2[C:26]([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])=[CH:27][CH2:28][S:29][C@H:24]12.C[Si](CC(N)=O)(C)C>C(Cl)Cl.CN(C)C=O>[CH:6]([NH:8][C:9]1[N:14]=[C:13]([C:15](=[N:19][O:20][CH3:21])[C:16]([NH:22][CH:23]2[C:43](=[O:44])[N:25]3[C:26]([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])=[CH:27][CH2:28][S:29][C@H:24]23)=[O:18])[CH:12]=[CH:11][CH:10]=1)=[O:7]

Participants

7

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylateHCID 543262512-(6-Formamidopyridin-2-yl)-2-methoxyiminoacetic acid

Product 1

HCID 1317122194-Nitrobenzyl 7-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylateYield 67.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of N,N-dimethylformamide (3 ml.) and phosphoryl chloride (460 mg.) was stirred at 37° to 40° C. for 30 minutes. To the solution were added methylene chloride (3 ml.) and 2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetic acid (669 mg.) at -20° to -25° C. and stirred at -10° to -15° C. for one hour. A solution of 4-nitrobenzyl 7-amino-3-cephem-4-carboxylate (670 mg.) and trimethylsilylacetamide (2 g.) in methylene chloride (200 ml.) was added to the above solution at -10° to -15° C., and then stirred at the same temperature for 30 minutes. After the solution was concentrated under reduced pressure, ethyl acetate and water were added to the residue. The ethyl acetate layer was separated, washed with an aqueous solution of sodium bicarbonate, water and a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was triturated with diethyl ether to give 4-nitrobenzyl 7-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (730 mg.), mp. 195° to 200° C. (dec.).

Workup

  1. stirringstirred at -10° to -15° C. for one hour
  2. stirringstirred at the same temperature for 30 minutes
  3. concentrationAfter the solution was concentrated under reduced pressure, ethyl acetate and water
  4. additionwere added to the residue
  5. customThe ethyl acetate layer was separated
  6. washwashed with an aqueous solution of sodium bicarbonate, water
  7. dry with materiala saturated aqueous solution of sodium chloride, dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-a52f0284196a45d9abc2d03c51be0dd2
Source dataset
uspto-grants-1983_07
Patent number
US04395411

Reaction notes

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