Sodium Chloride → 4-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-propoxyiminoacetamido]-3-cephem-4-carboxylate

HRID 1650502Notes

Reaction equation

HRID 1650502 reaction equation
P(Cl)(Cl)(Cl)=O.C[Si](CC(N)=O)(C)C.[NH2:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][CH2:27][CH3:28])[C:21]([OH:23])=O)[N:19]=1.[NH2:29][CH:30]1[C:50](=[O:51])[N:32]2[C:33]([C:37]([O:39][CH2:40][C:41]3[CH:46]=[CH:45][C:44]([N+:47]([O-:49])=[O:48])=[CH:43][CH:42]=3)=[O:38])=[CH:34][CH2:35][S:36][C@H:31]12.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+]>O1CCCC1.CC(C)=O.O.CN(C)C=O>[NH2:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][CH2:27][CH3:28])[C:21]([NH:29][CH:30]2[C:50](=[O:51])[N:32]3[C:33]([C:37]([O:39][CH2:40][C:41]4[CH:42]=[CH:43][C:44]([N+:47]([O-:49])=[O:48])=[CH:45][CH:46]=4)=[O:38])=[CH:34][CH2:35][S:36][C@H:31]23)=[O:23])[N:19]=1

Participants

11

Reactant 6

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylateHCID 540960402-(2-Amino-4-thiazolyl)-2-propoxyiminoacetic acid

Product 1

HCID 1317124554-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-propoxyiminoacetamido]-3-cephem-4-carboxylateYield 91.2%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Phosphoryl chloride (4.6 g.), trimethylsilylacetamide (0.95 g.) and N,N-dimethylformamide (1.2 g.) were added to a stirred suspension of 2-(2-amino-4-thiazolyl)-2-propoxyiminoacetic acid (syn isomer, 2.8 g.) in tetrahydrofuran (25 ml.) below 5° C., and stirred for 20 minutes. The solution was dropwise added to a suspension of 4-nitrobenzyl 7-amino-3-cephem-4-carboxylate (3.9 g.) in a mixture of tetrahydrofuran (20 ml.), water (20 ml.) and acetone (20 ml.) at -5° to 5° C. while keeping the pH value at 6.9 to 7.1 with 20% aqueous solution of sodium carbonate. The solution was stirred at -5° to 5° C. for 30 minutes and further at 10° C. for an hour, and adjusted to pH 7.5. After tetrahydrofuran (100 ml.) and a saturated aqueous solution of sodium chloride (200 ml.) were added to the resultant solution, the insoluble substance was filtered out. The organic layer was separated from the filtrate, washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was triturated with diisopropyl ether and the precipitates were collected by filtration to give 4-nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-propoxyiminoacetamido]-3-cephem-4-carboxylate (syn isomer, 5.8 g.).

Workup

  1. stirringThe solution was stirred at -5° to 5° C. for 30 minutes and further at 10° C. for an hour
  2. filtrationthe insoluble substance was filtered out
  3. customThe organic layer was separated from the filtrate
  4. washwashed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was triturated with diisopropyl ether
  8. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-ee5979b0dcdf48a2bdf8b36b6d23020b
Source dataset
uspto-grants-1990_05
Patent number
US04923998

Reaction notes

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