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

HRID 2412746Notes

Reaction equation

HRID 2412746 reaction equation
[CH2:1]([O:4][N:5]=[C:6]([C:10]1[N:11]=[C:12]([NH:15][CH:16]=[O:17])[S:13][CH:14]=1)[C:7]([OH:9])=O)[CH:2]=[CH2:3].C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[NH2:29][CH:30]1[C:50](=[O:51])[N:32]2[C:33]([C:47]([OH:49])=[O:48])=[C:34]([CH2:37][S:38][C:39]3[N:43]([CH2:44][CH:45]=[CH2:46])[N:42]=[N:41][N:40]=3)[CH2:35][S:36][C@H:31]12.C[Si](CC(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH2:1]([O:4][N:5]=[C:6]([C:10]1[N:11]=[C:12]([NH:15][CH:16]=[O:17])[S:13][CH:14]=1)[C:7]([NH:29][CH:30]1[C:50](=[O:51])[N:32]2[C:33]([C:47]([OH:49])=[O:48])=[C:34]([CH2:37][S:38][C:39]3[N:43]([CH2:44][CH:45]=[CH2:46])[N:42]=[N:41][N:40]=3)[CH2:35][S:36][C@H:31]12)=[O:9])[CH:2]=[CH2:3]

Participants

9

Reactant 5

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 542025522-Allyloxyimino-2-(2-formamidothiazol-4-yl)acetic acidHCID 704326537-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid

Product 1

HCID 1317125787-[2-allyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acidYield 79.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

2-Allyloxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer)(0.80 g) and dry ethyl acetate (10 ml) were added at 0° to 5° C. with stirring to a suspension of Vilsmeier reagent prepared from dry dimethylformamide (0.25 g) and phosphorus oxychloride (0.528 g) in dry ethyl acetate (0.75 ml) by conventional method, and the resulting mixture was stirred for 30 minutes at the same temperature to give an yellow solution. The solution was added at -10° C. with stirring to a solution of 7-amino-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (1.11 g) and trimethylsilylacetamide (2.96 g) in dry ethyl acetate (15 ml), and the mixture was stirred for 1.5 hours at the same temperature. After addition of water (15 ml) to the reaction mixture, the ethyl acetate layer was separated and extracted with an aqueous solution of sodium bicarbonate (30 ml). The aqueous extract was acifified to pH 2.0 with 10 % hydrochloric acid and extracted with ethyl acetate (150 ml). The extract was washed with water, dried and evaporated. The residue was pulverized with diisopropyl ether to give colorless powder of 7-[2-allyloxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1-allyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer)(1.48 g).

Workup

  1. customto give an yellow solution
  2. additionThe solution was added at -10° C.
  3. stirringthe mixture was stirred for 1.5 hours at the same temperature
  4. customthe ethyl acetate layer was separated
  5. extractionextracted with an aqueous solution of sodium bicarbonate (30 ml)
  6. extractionThe aqueous extract
  7. extractionextracted with ethyl acetate (150 ml)
  8. washThe extract was washed with water
  9. customdried
  10. customevaporated

Sources & evidence

ORD record
ord-c02fc9b5f3ef46a19f79ee24ef87b277
Source dataset
uspto-grants-1985_01
Patent number
US04493833

Reaction notes

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