Hydrochloric Acid → HCID 131713431, compound

HRID 1982732Notes

Reaction equation

HRID 1982732 reaction equation
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[CH:12]([NH:14][C:15]1[S:16][C:17]([Cl:34])=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:21]([OH:23])=O)[N:19]=1)=[O:13].[NH2:35][CH:36]1[C:46](=[O:47])[N:38]2[C:39]([C:43]([OH:45])=[O:44])=[CH:40][CH2:41][S:42][C@H:37]12.C[Si](C)(C)NC(=O)C.C(=O)(O)[O-].[Na+].Cl>O1CCCC1.C(Cl)Cl.C(OCC)(=O)C.O.CN(C)C=O>[CH:12]([NH:14][C:15]1[S:16][C:17]([Cl:34])=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[C:21]([NH:35][CH:36]2[C:46](=[O:47])[N:38]3[C:39]([C:43]([OH:45])=[O:44])=[CH:40][CH2:41][S:42][C@H:37]23)=[O:23])[N:19]=1)=[O:13]

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 24813Phosphorus oxychlorideHCID 25989Acetamide, N-(trimethylsilyl)-HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 516892Sodium BicarbonateHCID 12941984(6R)-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 540757552-(2-Formamido-5-chlorothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid

Product 1

HCID 131713431HCID 131713431, compoundYield 87%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Vilsmeier reagent prepared from N,N-dimethylformamide (0.46 ml) and phosphorous oxychloride (0.55 ml) was suspended in dry tetrahydrofuran (20 ml). To the suspension was added 2-(2-formamido-5-chlorothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetic acid (syn isomer) (1.8 g) under ice-cooling with stirring and then the solution was stirred at the same temperature for an hour to prepare the activated acid solution. To the solution of 7-amino-3-cephem-4-carboxylic acid (1.1 g) and N-trimethylsilylacetamide (6.5 g) in methylene chloride (20 ml) was added the activated acid solution obtained above all at once at -20° C., and the solution was stirred at -20° C. to -10° C. for an hour. After water and ethyl acetate were added to the resultant solution, the mixed solution was adjusted to pH 7.3 with a saturated aqueous solution of sodium bicarbonate. Then the aqueous layer was adjusted to pH 2.0 with conc. hydrochloric acid, extracted with mixed solvent of ethyl acetate (100 ml) and tetrahydrofuran (50 ml). The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. After removing the solvent, diisopropyl ether was added to the residue. The insoluble residue was collected by filtration to give 7-[2-(2-formamido-5-chlorothiazol-4-yl)-2-tert-butoxycarbonylmethoxyiminoacetamido]-3-cephem-4-carboxylic acid (syn isomer) (2.35 g), mp 145° to 149° C. (dec.).

Workup

  1. temperaturecooling
  2. stirringthe solution was stirred at the same temperature for an hour
  3. customto prepare the activated acid solution
  4. customobtained above all at once at -20° C.
  5. stirringthe solution was stirred at -20° C. to -10° C. for an hour
  6. extractionextracted with mixed solvent of ethyl acetate (100 ml) and tetrahydrofuran (50 ml)
  7. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. customAfter removing the solvent, diisopropyl ether
  10. additionwas added to the residue
  11. filtrationThe insoluble residue was collected by filtration

Sources & evidence

ORD record
ord-236c8cb2f5324971b40c34ed27e557fd
Source dataset
uspto-grants-1986_06
Patent number
US04596829

Reaction notes

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