Chloride → 7-[2-(2-formamidothiazol-4-yl)-2-(2-chloroethoxyimino)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 255790Notes

Reaction equation

HRID 255790 reaction equation
[CH3:1][N:2]([CH3:5])[CH:3]=O.[Cl-:6].[CH:7]([NH:9][C:10]1[S:11][CH:12]=[C:13]([C:15](=[N:19][O:20][CH2:21][CH2:22][Cl:23])[C:16]([OH:18])=O)[N:14]=1)=[O:8].[NH2:24][CH:25]1[C:45](=[O:46])[N:27]2[C:28]([C:42]([OH:44])=[O:43])=[C:29]([CH2:32][S:33][C:34]3[N:38]([CH2:39][CH:40]=[CH2:41])[N:37]=[N:36][N:35]=3)[CH2:30][S:31][C@H:26]12>C(OCC)(=O)C.O>[CH3:1][N+:2]([CH3:5])=[CH:3][Cl:23].[Cl-:6].[CH:7]([NH:9][C:10]1[S:11][CH:12]=[C:13]([C:15](=[N:19][O:20][CH2:21][CH2:22][Cl:23])[C:16]([NH:24][CH:25]2[C:45](=[O:46])[N:27]3[C:28]([C:42]([OH:44])=[O:43])=[C:29]([CH2:32][S:33][C:34]4[N:38]([CH2:39][CH:40]=[CH2:41])[N:37]=[N:36][N:35]=4)[CH2:30][S:31][C@H:26]23)=[O:18])[N:14]=1)=[O:8]

Participants

8

Reactant 4

HCID 312ChlorideHCID 6228DimethylformamideHCID 539721442-(2-Formamidothiazol-4-yl)-2-(2-chloroethoxyimino)acetic acidHCID 704326537-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 2

HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 1317153227-[2-(2-formamidothiazol-4-yl)-2-(2-chloroethoxyimino)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 83.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent was prepared from dry N,N-dimethylformamide (0.3 g.) and phosphory chloride (0.5 g.) in dry ethyl acetate (1.2 ml.) in a usual manner. 2-(2-Formamidothiazol-4-yl)-2-(2-chloroethoxyimino)acetic acid (syn isomer, 0.9 g.) and dry ethyl acetate (10 ml.) were added to the mixture under ice-cooling and then stirred at the same temperature for 30 minutes. [Solution A]Trimethylsilylacetamide (2.9 g.) was added to a solution of 7-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.0 g.) in dry ethyl acetate (20 ml.) and stirred at 40° C. for 30 minutes. To the solution was added the solution A at -10° C. and stirred at -5°to -10° C. for an hour. Water was added to the resultant solution and the organic layer was separated. Water was added to the organic layer and adjusted to pH 7.0 with sodium carbonate. The aqueous layer was separated, washed with ethyl acetate and adjusted to pH 4.5 with 10% hydrochloric acid. The solution was extracted with ethyl acetate. The extract was washed with a sodium chloride saturated aqueous solution, dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diisopropyl ether. The precipitates were collected by filtration, washed with diisopropyl ether and dried to give 7-[2-(2-formamidothiazol-4-yl)-2-(2-chloroethoxyimino)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 0.83 g.).

Workup

  1. temperaturecooling
  2. stirringstirred at 40° C. for 30 minutes
  3. stirringstirred at -5°to -10° C. for an hour
  4. customthe organic layer was separated
  5. additionWater was added to the organic layer and adjusted to pH 7.0 with sodium carbonate
  6. customThe aqueous layer was separated
  7. washwashed with ethyl acetate
  8. extractionThe solution was extracted with ethyl acetate
  9. washThe extract was washed with a sodium chloride saturated aqueous solution
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated in vacuo
  12. filtrationThe precipitates were collected by filtration
  13. washwashed with diisopropyl ether
  14. customdried

Sources & evidence

ORD record
ord-b3edc3e410a14f5fb5177a1aa170de53
Source dataset
uspto-grants-1987_10
Patent number
US04698337

Reaction notes

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