Hydrochloric Acid → (6R)-8-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 18691

Reaction equation

HRID 18691 reaction equation
N[CH:2]1[C:24](=[O:25])[N:4]2[C:5]([C:21]([OH:23])=[O:22])=[C:6](CSC3N(CS(O)(=O)=O)N=NN=3)[CH2:7][S:8][C@H:3]12.[OH-].[Na+].C(=O)(O)[O-].[Na+].Cl.C(O)(=O)C.C(O)(=O)C.[CH:42]1([NH:48][CH2:49][CH2:50][NH:51][CH:52]2[CH2:57][CH2:56][CH2:55][CH2:54][CH2:53]2)[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1>O.C(O)(C)C>[CH:52]1([NH:51][CH2:50][CH2:49][NH:48][CH:42]2[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]2)[CH2:53][CH2:54][CH2:55][CH2:56][CH2:57]1.[S:8]1[C@@H:3]2[CH2:2][C:24](=[O:25])[N:4]2[C:5]([C:21]([OH:23])=[O:22])=[CH:6][CH2:7]1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium Bicarbonate2×HCID 85594586N,N'-dicyclohexylethylenediamine diacetateHCID 875069217-Amino-3-(sulfomethyl-1h-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 2

HCID 273886N,N'-Dicyclohexyl-1,2-ethanediamineHCID 52921562(6R)-8-Oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 286.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
7.5 °C

Procedure

7-amino-3-(sulfomethyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (5 g), was dissolved in water (19 ml) using 30% w/w sodium hydroxide (1.5 g in 8 ml water) and sodium bicarbonate (1 g), O-formylmandeloyl chloride (2.45 g) was added at 0-5° C. and maintained at 5-10° C. over a period of 1-2 hours. After the completion of reaction, the reaction mixture was acidified with conc. HCl (2.6 g) and maintained the reaction at 28-30° C. for about 2-3 hours. After the completion of reaction, sodium bicarbonate (˜3.5 g) was added to set the pH 5±1 and the solution was added to a solution of N,N′-dicyclohexylethylenediamine diacetate (9.26 g) in water (40 mL) and isopropyl alcohol (40 mL) and stirred well at 25-30° C. for about 2-3 hours. The reaction mixture was cooled to 5-10° C., filtered, washed with chilled water (0-5° C.) and isopropyl alcohol (0-5° C.) and dried the material under vacuum at ˜40° C. to get N,N′-dicyclohexylethylenediamine salt of 7-D-mandelamido-3-(1-sulfomethyl-1H-tetrazol-5-yl)thio)methyl)-3-cephem-4-carboxylic acid (6.5 g). Step-(ii)

Workup

  1. additionwas added at 0-5° C.
  2. customAfter the completion of reaction
  3. temperaturemaintained
  4. customthe reaction at 28-30° C. for about 2-3 hours
  5. additionwas added
  6. temperatureThe reaction mixture was cooled to 5-10° C.
  7. filtrationfiltered
  8. washwashed with chilled water (0-5° C.) and isopropyl alcohol (0-5° C.)
  9. customdried the material under vacuum at ˜40° C.

Sources & evidence

ORD record
ord-a4e3c7d5b2f8495a9dd1924f570b4cfa
Source dataset
uspto-grants-2010_06
Patent number
US07741478B2

Linked notes

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