Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-isobutoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate

HRID 1074792Notes

Reaction equation

HRID 1074792 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[NH2:44][CH:45]1[C:66](=[O:67])[N:47]2[C:48]([C:53]([O:55][CH2:56][C:57]3[CH:62]=[CH:61][C:60]([N+:63]([O-:65])=[O:64])=[CH:59][CH:58]=3)=[O:54])=[C:49]([OH:52])[CH2:50][S:51][C@H:46]12>C(OCC)(=O)C.O.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]([NH:44][CH:45]2[C:66](=[O:67])[N:47]3[C:48]([C:53]([O:55][CH2:56][C:57]4[CH:58]=[CH:59][C:60]([N+:63]([O-:65])=[O:64])=[CH:61][CH:62]=4)=[O:54])=[C:49]([OH:52])[CH2:50][S:51][C@H:46]23)=[O:12])[N:8]=1)=[O:2]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 539625342-(2-Formamidothiazol-4-yl)-2-isobutoxyiminoacetic acidHCID 681232354-Nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate

Product 1

HCID 1317124724-Nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-isobutoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylateYield 90.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
40 °C

Procedure

2-(2-Formamidothiazol-4-yl)-2-isobutoxyiminoacetic acid (syn isomer, 0.54 g.), N,N-dimethylformamide (0.16 g.) phosphoryl chloride (0.34 g.) and ethyl acetate (10 ml.) were treated in a similar manner to that of Example 15-(1) to give the activated acid solution. On the other hand, trimethylsilylacetamide (1.85 g.) and bis(trimethylsilyl)acetamide (1.62 g.) were added to a suspension of 4-nitrobenzyl 7-amino-3-hydroxy-3-cephem-4-carboxylate (0.7 g.) in ethyl acetate (10 ml.) and stirred at 40° C. for 30 minutes. The activated acid solution obtained above was added to the solution at -20° C. all at once, and stirred at the same temperature for an hour. Water (10 ml.) was added to the resultant solution, and the organic layer was separated, washed with water, an aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and then dried. After the solution was concentrated in vacuo, the residue was pulverized with diisopropyl ether. The precipitates were collected by filtration, washed with diisopropyl ether and dried to give 4-nitrobenzyl 7-[2-(2-formamidothiazol-4-yl)-2-isobutoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate (syn isomer, 1.09 g.).

Workup

  1. customto give the activated acid solution
  2. customThe activated acid solution obtained
  3. additionabove was added to the solution at -20° C. all at once, and
  4. stirringstirred at the same temperature for an hour
  5. customthe organic layer was separated
  6. washwashed with water
  7. dry with materialan aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, and then dried
  8. concentrationAfter the solution was concentrated in vacuo
  9. filtrationThe precipitates were collected by filtration
  10. washwashed with diisopropyl ether
  11. customdried

Sources & evidence

ORD record
ord-46e5a9fbe48545558fb2747171d1a6b0
Source dataset
uspto-grants-1983_07
Patent number
US04393059

Reaction notes

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