Phosphorus oxychloride → HCID 131713185, compound

HRID 905454Notes

Reaction equation

HRID 905454 reaction equation
[NH2:1][C:2]1[O:6][N:5]=[C:4]([C:7](=[N:11][O:12][CH3:13])[C:8]([OH:10])=O)[N:3]=1.P(Cl)(Cl)(Cl)=O.Cl.[NH2:20][CH:21]1[C:46](=[O:47])[N:23]2[C:24]([C:30]([O:32][CH:33]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=3)=[O:31])=[C:25]([CH:28]=[CH2:29])[CH2:26][S:27][C@H:22]12.C[Si](CC(N)=O)(C)C>C(Cl)Cl.C(OCC)(=O)C.O.CN(C)C=O>[NH2:1][C:2]1[O:6][N:5]=[C:4]([C:7](=[N:11][O:12][CH3:13])[C:8]([NH:20][CH:21]2[C:46](=[O:47])[N:23]3[C:24]([C:30]([O:32][CH:33]([C:34]4[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=4)[C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)=[O:31])=[C:25]([CH:28]=[CH2:29])[CH2:26][S:27][C@H:22]23)=[O:10])[N:3]=1

Participants

9

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12818005Benzhydryl 7-amino-3vinyl-3cephem-4-carboxylate hydrochlorideHCID 54161649HCID 54161649, compound

Product 1

HCID 131713185HCID 131713185, compoundYield 39.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

To a suspension of 2-(5-amino-1,2,4-oxadiazol-3-yl)-2-methoxyiminoacetic acid (syn isomer) (2.23 g) in methylene chloride (70 ml) was added phosphorus oxychloride (7.2 g), followed by stirring at ambient temperature for 45 minutes. Thereto was added N,N-dimethylformamide (4.4 g) at -10° C., and the mixture was stirred at -10° to 0° C. for an hour to prepare the activated acid solution. This solution was added to a solution of benzhydryl 7-amino-3-vinyl-3-cephem-4-carboxylate hydrochloride (4.7 g) and trimethylsilylacetamide (8.6 g) in ethyl acetate (50 ml) at -20° C., and the mixture was stirred at -20° to 0° C. for an hour. After ethyl acetate (200 ml) and water (200 ml) were added to the reaction mixture, the ethyl acetate layer was separated out, washed with a saturated aqueous sodium bicarbonate and an aqueous sodium chloride, and then dried over anhydrous magnesium sulfate. Removal of the solvent gave a residue, which was chromatographed on silica gel eluting with a mixed solvent of ethyl acetate and benzene (6:4 by volume). Fractions containing a desired compound firstly eluted were collected and evaporated to obtain benzhydryl 7-[2-(5-amino-1,2,4-oxadiazol-3-yl)-2-methoxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer) (2.4 g).

Workup

  1. stirringthe mixture was stirred at -10° to 0° C. for an hour
  2. customto prepare the activated acid solution
  3. stirringthe mixture was stirred at -20° to 0° C. for an hour
  4. customthe ethyl acetate layer was separated out
  5. washwashed with a saturated aqueous sodium bicarbonate
  6. dry with materialan aqueous sodium chloride, and then dried over anhydrous magnesium sulfate
  7. customRemoval of the solvent
  8. customgave a residue, which
  9. customwas chromatographed on silica gel eluting with a mixed solvent of ethyl acetate and benzene (6:4 by volume)
  10. additionFractions containing a desired compound
  11. washfirstly eluted
  12. customwere collected
  13. customevaporated

Sources & evidence

ORD record
ord-a787f0647e3647c594800a61bd459025
Source dataset
uspto-grants-1983_12
Patent number
US04423213

Reaction notes

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