Phosphorus oxychloride → 4-Nitrobenzyl 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-cephem-4-carboxylate

HRID 615767Notes

Reaction equation

HRID 615767 reaction equation
P(Cl)(Cl)(Cl)=O.[O:6]1[C:11]([C:12](=[N:16][O:17][CH2:18][CH2:19][CH3:20])[C:13]([OH:15])=O)=[CH:10][S:9][CH2:8][CH2:7]1.[NH2:21][CH:22]1[C:42](=[O:43])[N:24]2[C:25]([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:30])=[CH:26][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>[O:6]1[C:11]([C:12](=[N:16][O:17][CH2:18][CH2:19][CH3:20])[C:13]([NH:21][CH:22]2[C:42](=[O:43])[N:24]3[C:25]([C:29]([O:31][CH2:32][C:33]4[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=4)=[O:30])=[CH:26][CH2:27][S:28][C@H:23]23)=[O:15])=[CH:10][S:9][CH2:8][CH2:7]1

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylateHCID 537836602-(2,3-Dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid

Product 1

HCID 1317120154-Nitrobenzyl 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-cephem-4-carboxylateYield 83.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

Dry N,N-dimethylformamide (1.26 ml.), phosphoryl chloride (1.48 ml.), 2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetic acid (syn isomer, 3.48 g.) and dry ethyl acetate (5 ml.) were treated in a conventional manner to give an activated acid solution. On the other hand, a solution of 4-nitrobenzyl 7-amino-3-cephem-4-carboxylate (5.0 g.) trimethylsilylacetamide (12.6 g.) and bis(trimethylsilyl)acetamide (8.3 g.) in ethyl acetate (700 ml.) was stirred at 40° C. for an hour. The activated acid solution was added all at once to the solution at -30° C. and stirred at -10° to -30° C. for 2 hours. After adding water (50 ml.) to the resultant solution, the ethyl acetate layer was separated. The solution was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diisopropyl ether, and the precipitates were collected by filtration and washed with diisopropyl ether to give 4-nitrobenzyl 7-[2-(2,3-dihydro-1,4-oxathiin-6-yl)-2-n-propoxyiminoacetamido]-3-cephem-4-carboxylate (syn isomer, 6.80 g.).

Workup

  1. customto give an activated acid solution
  2. additionThe activated acid solution was added all at once to the solution at -30° C.
  3. customthe ethyl acetate layer was separated
  4. washThe solution was washed with a saturated aqueous solution of sodium bicarbonate
  5. dry with materiala saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. filtrationthe precipitates were collected by filtration
  8. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-c0b8d79500f24ab99308b75bde299097
Source dataset
uspto-grants-1985_02
Patent number
US04500709

Reaction notes

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