Phosphorus oxychloride → 7-[2-(2-Formamidothiazol-4-yl)-2-(2,2,2-trifluoroethyoxyimino)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 255778Notes

Reaction equation

HRID 255778 reaction equation
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[C:21]([OH:23])=O)[N:19]=1)=[O:13].[NH2:31][CH:32]1[C:49](=[O:50])[N:34]2[C:35]([C:46]([OH:48])=[O:47])=[C:36]([CH2:39][S:40][C:41]3[S:42][CH:43]=[N:44][N:45]=3)[CH2:37][S:38][C@H:33]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH:12]([NH:14][C:15]1[S:16][CH:17]=[C:18]([C:20](=[N:24][O:25][CH2:26][C:27]([F:30])([F:29])[F:28])[C:21]([NH:31][CH:32]2[C:49](=[O:50])[N:34]3[C:35]([C:46]([OH:48])=[O:47])=[C:36]([CH2:39][S:40][C:41]4[S:42][CH:43]=[N:44][N:45]=4)[CH2:37][S:38][C@H:33]23)=[O:23])[N:19]=1)=[O:13]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 128891877-Amino-3-(1,3,4-thiadiazol-2-ylthiomethyl)-3cephem-4-carboxylic acidHCID 540184582-(2,2,2-Trifluoroethoxyimino)-2-(2-formylaminothiazol-4-yl)acetic acid

Product 1

HCID 1317153087-[2-(2-Formamidothiazol-4-yl)-2-(2,2,2-trifluoroethyoxyimino)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acidYield 78.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Vilsmeier reagent prepared from N,N-dimethyl formamide (0.2 g.) and phosphoryl chloride (0.42 g.) in a conventional manner was added to ethyl acetate (10 ml.), and then 2-(2-formamidothiazol-4-yl)-2-(2,2,2-trifluoroethoxyimino)acetic acid (syn isomer, 0.75 g.) was added to the solution under ice-cooling and stirred at the same temperature for 30 minutes. The solution was added to a solution of 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (0.83 g.) and trimethylsilylacetamide (2.62 g.) in ethyl acetate (30 ml.) at -30° C., and stirred at the same temperature for 1.5 hours. After adding ethyl acetate (100 ml.) and water to the resultant solution, the ethyl acetate layer was separated. Water (100 ml.) was added to the ethyl acetate solution adjusted to pH 7.5 with saturated aqueous solution of sodium bicarbonate. The aqueous layer was separated and the ethyl acetate (150 ml.) was added thereto, and adjusted to pH 1.5 with hydrochloric acid. The ethyl acetate layer was separated, washed with saturated aqueous solution of sodium chloride, dried over magnesium sulfate, and concentrated in vacuo. The residue was triturated with diethyl ether to give 7-[2-(2-formamidothiazol-4-yl)-2-(2,2,2-trifluoroethyoxyimino)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 1.2 g.).

Workup

  1. temperaturecooling
  2. stirringstirred at the same temperature for 1.5 hours
  3. customthe ethyl acetate layer was separated
  4. additionWater (100 ml.) was added to the ethyl acetate solution
  5. customThe aqueous layer was separated
  6. additionthe ethyl acetate (150 ml.) was added
  7. customThe ethyl acetate layer was separated
  8. washwashed with saturated aqueous solution of sodium chloride
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was triturated with diethyl ether

Sources & evidence

ORD record
ord-8c9250b0a03140c28b9b53846b580182
Source dataset
uspto-grants-1987_10
Patent number
US04698337

Reaction notes

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