Hydrochloric Acid → 7beta-[2-Cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(5,6-dioxo-2-methyl-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 1074349Notes

Reaction equation

HRID 1074349 reaction equation
[NH2:1][C@@H:2]1[C:23](=[O:24])[N:4]2[C:5]([C:20]([OH:22])=[O:21])=[C:6]([CH2:9][S:10][C:11]3[N:12]([CH3:19])[NH:13][C:14](=[O:18])[C:15](=[O:17])[N:16]=3)[CH2:7][S:8][C@H:3]12.C(=O)(O)[O-].[Na+].[CH:30]1([O:33][N:34]=[C:35]([C:39]2[N:40]=[C:41]([NH:44][CH:45]=[O:46])[S:42][CH:43]=2)[C:36](O)=[O:37])[CH2:32][CH2:31]1.Cl>O1CCCC1.O.C(OCC)(=O)C>[CH:30]1([O:33][N:34]=[C:35]([C:39]2[N:40]=[C:41]([NH:44][CH:45]=[O:46])[S:42][CH:43]=2)[C:36]([NH:1][C@@H:2]2[C:23](=[O:24])[N:4]3[C:5]([C:20]([OH:22])=[O:21])=[C:6]([CH2:9][S:10][C:11]4[N:12]([CH3:19])[NH:13][C:14](=[O:18])[C:15](=[O:17])[N:16]=4)[CH2:7][S:8][C@H:3]23)=[O:37])[CH2:32][CH2:31]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium Bicarbonate2×HCID 6351062(6R-trans)-7-Amino-8-oxo-3-(((1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio)methyl)-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidHCID 540072742-Cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid

Product 1

HCID 1317167217beta-[2-Cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(5,6-dioxo-2-methyl-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thiomethyl-3-cephem-4-carboxylic acidYield 57.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 7β-amino-3-(5,6-dioxo-2-methyl-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thiomethyl-3-cephem-4-carboxylic acid (966 mg) and sodium bicarbonate (437 mg) in a mixture of tetrahydrofuran (10 ml) and water (10 ml) was dropwise added the activated acid solution, prepared from 2-cyclopropyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (500 mg) according to a similar manner to that described in Example 1, with stirring and keeping pH 7.0 to 8.0 with saturated aqueous solution of sodium bicarbonate at 0° to 5° C. The mixture was stirred for 20 minutes at the same temperature. To the mixture was added ethyl acetate (40 ml) and the mixture was adjusted to pH 1.5 with 6N hydrochloric acid. The resulting insoluble material was filtered off. The organic layer was separated from the filtrate, dried over magnesium sulfate and concentrated in vacuo. The residue was triturated with diethyl ether to give 7β-[2-cyclopropyloxyimino-2 -(2-formamidothiazol-4-yl)acetamido]-3-(5,6-dioxo-2-methyl-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (685 mg).

Workup

  1. additionwas dropwise added the activated acid solution
  2. customat 0° to 5° C
  3. stirringThe mixture was stirred for 20 minutes at the same temperature
  4. filtrationThe resulting insoluble material was filtered off
  5. customThe organic layer was separated from the filtrate
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-71aaa01041974826bb32dc1b4488d7b8
Source dataset
uspto-grants-1990_11
Patent number
US04973699

Reaction notes

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