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

HRID 1650501Notes

Reaction equation

HRID 1650501 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][CH:26]([CH3:28])[CH3:27])[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+].[Cl-].[Na+]>O1CCCC1.O.CN(C)C=O>[NH2:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH:26]([CH3:28])[CH3:27])[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

10

Reactant 6

HCID 5234Sodium ChlorideHCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-2×HCID 516892Sodium BicarbonateHCID 12775080p-Nitrobenzyl 7-amino-3-cephem-4-carboxylateHCID 541000552-Isopropoxyimino-2-(2-aminothiazol-4-yl)acetic acid

Product 1

HCID 1317124544-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-isopropoxyiminoacetamido]-3-cephem-4-carboxylateYield 94.4%

Reagents, catalysts & solvents 3

HCID 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-isopropoxyiminoacetic acid (syn isomer, 2.8 g.) in tetrahydrofuran (25 ml.) below 5° C. for 30 minutes [Solution A]. On the other hand, trimethylsilylacetamide (10.5 g.) was added to a suspension of 4-nitrobenzyl 7-amino-3-cephem-4-carboxylate (3.9 g.) in tetrahydrofuran (50 ml.), and stirred at room temperature for 1.5 hours. To the solution was added the above solution A at -20° C. all at once, and the solution was stirred at -5° to 0° C. for 40 minutes. Water (70 ml.) and tetrahydrofuran (100 ml.) were added to the resultant solution at -20° C. The solution was adjusted to pH 7.5 with an aqueous solution of sodium bicarbonate and stirred for an hour. After a saturated aqueous solution of sodium chloride (200 ml.) was added, the organic layer was separated. The remaining aqueous layer was extracted with tetrahydrofuran, and the extract and the above organic layer were combined, 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-isopropoxyiminoacetamido]-3-cephem-4-carboxylate (syn isomer, 6.0 g.).

Workup

  1. stirringwas stirred at -5° to 0° C. for 40 minutes
  2. stirringstirred for an hour
  3. customthe organic layer was separated
  4. extractionThe remaining aqueous layer was extracted with tetrahydrofuran
  5. extractionthe extract
  6. washwashed with a saturated aqueous solution of sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was triturated with diisopropyl ether
  10. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-ec5114c7b4ab47058fb813a45583fe0d
Source dataset
uspto-grants-1990_05
Patent number
US04923998

Reaction notes

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