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

HRID 1650500Notes

Reaction equation

HRID 1650500 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][CH3:27])[C:21]([OH:23])=O)[N:19]=1.Cl.[NH2:29][CH:30]1[C:51](=[O:52])[N:32]2[C:33]([C:38]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][C:45]([N+:48]([O-:50])=[O:49])=[CH:44][CH:43]=3)=[O:39])=[C:34]([Cl:37])[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][CH2:26][CH3:27])[C:21]([NH:29][CH:30]2[C:51](=[O:52])[N:32]3[C:33]([C:38]([O:40][CH2:41][C:42]4[CH:43]=[CH:44][C:45]([N+:48]([O-:50])=[O:49])=[CH:46][CH:47]=4)=[O:39])=[C:34]([Cl:37])[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 534242352-(2-Amino-4-thiazolyl)-2-ethoxyiminoacetic acidHCID 703621504-Nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride

Product 1

HCID 1317124534-Nitrobenzyl 7-[2-(2-amino-4-thiazolyl)-2-ethoxyimino-acetamido]-3-chloro-3-cephem-4-carboxylateYield 75.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

Phosphoryl chloride (1.76 g.) and trimethylsilylacetamide (0.4 g.) were added to a stirred suspension of 2-(2-amino-4-thiazolyl)-2-ethoxyiminoacetic acid (syn isomer, 1.0 g) in tetrahydrofuran (10 ml.) below 5° C., and stirred at the same temperature for 30 minutes. N,N-Dimethylformamide (0.4 g.) was added to the solution and stirred below 5° C. for 20 minutes [Solution A]. Trimethylsilylacetamide (4.8 g.) was added to a stirred suspension of 4-nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate hydrochloride (1.9 g.) in tetrahydrofuran (15 ml.), and the solution was stirred at room temperature for an hour. To the solution was added the above Solution A all at once at -20° C., and the solution was stirred at 0° C. for an hour. Water (50 ml.) was added to the resultant solution at -20° C., and adjusted to pH 8.0 with an aqueous solution of sodium bicarbonate. Tetrahydrofuran (50 ml.) and a saturated aqueous solution of sodium chloride (50 ml.) were added to the solution. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After concentrating the solution 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-ethoxyiminoacetamido]-3-chloro-3-cephem-4-carboxylate (syn isomer, 2.0 g.).

Workup

  1. stirringthe solution was stirred at room temperature for an hour
  2. stirringthe solution was stirred at 0° C. for an hour
  3. customThe organic layer was separated
  4. washwashed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. concentrationAfter concentrating the solution under reduced pressure
  7. customthe residue was triturated with diisopropyl ether
  8. filtrationthe precipitates were collected by filtration

Sources & evidence

ORD record
ord-25321a31dbb343918f033fe9f8eb58fb
Source dataset
uspto-grants-1990_05
Patent number
US04923998

Reaction notes

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