Phosphorus oxychloride → 7-[2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-methyl-3-cephem-4-carboxylic acid

HRID 255767Notes

Reaction equation

HRID 255767 reaction equation
[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH2:16][O:17][CH:18]=[O:19])[C:10]([OH:12])=O)[N:8]=1)=[O:2].P(Cl)(Cl)(Cl)=O.[NH2:25][CH:26]1[C:37](=[O:38])[N:28]2[C:29]([C:34]([OH:36])=[O:35])=[C:30]([CH3:33])[CH2:31][S:32][C@H:27]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH:1]([NH:3][C:4]1[S:5][CH:6]=[C:7]([C:9](=[N:13][O:14][CH2:15][CH2:16][O:17][CH:18]=[O:19])[C:10]([NH:25][CH:26]2[C:37](=[O:38])[N:28]3[C:29]([C:34]([OH:36])=[O:35])=[C:30]([CH3:33])[CH2:31][S:32][C@H:27]23)=[O:12])[N:8]=1)=[O:2]

Participants

8

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 13475828(6R)-7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidHCID 541333172-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetic acid

Product 1

HCID 1317152957-[2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-methyl-3-cephem-4-carboxylic acidYield 46.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

2-(2-Formamidothiazol-4-yl)-2-(2-formyloxyethoxyimino)acetic acid (syn isomer 2.9 g.), N,N-dimethylformamide (0.8 g.), phosphoryl chloride (1.7 g.) and dry ethyl acetate (23 ml.) were treated in a similar manner to that of the Example 1-(1) to give an activated acid solution. The solution was added to a solution of 7-amino-3-methyl-3-cephem-4-carboxylic acid (2.0 g.) and trimethylsilylacetamide (8.6 g.) in dry ethyl acetate (40 ml.) at -10° C. and stirred at the same temperature for an hour. After adding water (30 ml.) to the reaction mixture, the organic layer was separated and extracted with an aqueous solution of sodium bicarbonate (30 ml.). The extract was adjusted to pH 2.5 with conc. hydrochloric acid and extracted with ethyl acetate (50 ml.). The extract was washed with a saturated aqueous solution of sodium chloride, dried and evaporated in vacuo. The residue was triturated with diisopropyl ether to give 7-[2-(2-formamidothiazol- 4-yl)-2-(2-formyloxyethoxyimino)acetamido]-3-methyl-3-cephem-4-carboxylic acid (syn isomer, 2.10 g.).

Workup

  1. customto give an activated acid solution
  2. customthe organic layer was separated
  3. extractionextracted with an aqueous solution of sodium bicarbonate (30 ml.)
  4. extractionextracted with ethyl acetate (50 ml.)
  5. washThe extract was washed with a saturated aqueous solution of sodium chloride
  6. customdried
  7. customevaporated in vacuo
  8. customThe residue was triturated with diisopropyl ether

Sources & evidence

ORD record
ord-196657a7fe014c7aa62218d9283d953a
Source dataset
uspto-grants-1987_10
Patent number
US04698337

Reaction notes

Loading…