Phosphorus oxychloride → HCID 131712600, compound

HRID 1659785Notes

Reaction equation

HRID 1659785 reaction equation
[CH2:1]([O:3][N:4]=[C:5]([C:9]1[N:10]=[C:11]([NH:14][CH:15]=[O:16])[S:12][CH:13]=1)[C:6]([OH:8])=O)[CH3:2].C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.[NH2:28][CH:29]1[C:46](=[O:47])[N:31]2[C:32]([C:43]([OH:45])=[O:44])=[C:33]([CH2:36][S:37][C:38]3[S:39][CH:40]=[N:41][N:42]=3)[CH2:34][S:35][C@H:30]12.C[Si](CC(N)=O)(C)C.C[Si](C([Si](C)(C)C)C(N)=O)(C)C>C(OCC)(=O)C.O.CN(C)C=O>[CH2:1]([O:3][N:4]=[C:5]([C:9]1[N:10]=[C:11]([NH:14][CH:15]=[O:16])[S:12][CH:13]=1)[C:6]([NH:28][CH:29]1[C:46](=[O:47])[N:31]2[C:32]([C:43]([OH:45])=[O:44])=[C:33]([CH2:36][S:37][C:38]3[S:39][CH:40]=[N:41][N:42]=3)[CH2:34][S:35][C@H:30]12)=[O:8])[CH3:2]

Participants

10

Reactant 6

HCID 24813Phosphorus oxychlorideHCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 11708267BistrimethylsilylacetamidHCID 128891877-Amino-3-(1,3,4-thiadiazol-2-ylthiomethyl)-3cephem-4-carboxylic acidHCID 544580772-(2-Formamidothiazol-4-yl)-2-ethoxyiminoacetic acid

Product 1

HCID 131712600HCID 131712600, compoundYield 37%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

2-Ethoxyimino-2-(2-formamidothiazol-4-yl)acetic acid (syn isomer) (3.0 g.) and dry ethyl acetate (40 ml.) were added at 0° to 5° C. with stirring to a suspension of Vilsmeier reagent prepared from dry dimethylformamide (1.0 g.) and phosphorus oxychloride (2.1 g.) in dry ethyl acetate (4.0 ml.) by conventional method, and the resulting mixture was stirred for 30 minutes at the same temperature. The solution was added at -10° C. with stirring to a solution of 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (3.7 g.), trimethylsilylacetamide (10.3 g.) and bis-(trimethylsilyl)acetamide (6.8 g.) in dry ethyl acetate (80 ml.), and the mixture was stirred for 1.5 hours at the same temperature. After addition of water (50 ml.) to the reaction mixture, an insoluble material was filtered off, the ethyl acetate layer in the filtrate was separated and extracted with an aqueous solution of sodium bicarbonate (50 ml.). The aqueuous extract was washed with ethyl acetate and acidified to pH 2.0 with conc. hydrochloric acid. Precipitates were collected by filtration, washed with water and dried to give powder of 7-[2-ethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (2.3 g.).

Workup

  1. additionThe solution was added at -10° C.
  2. stirringthe mixture was stirred for 1.5 hours at the same temperature
  3. filtrationan insoluble material was filtered off
  4. customthe ethyl acetate layer in the filtrate was separated
  5. extractionextracted with an aqueous solution of sodium bicarbonate (50 ml.)
  6. extractionThe aqueuous extract
  7. washwas washed with ethyl acetate
  8. customPrecipitates
  9. filtrationwere collected by filtration
  10. washwashed with water
  11. customdried

Sources & evidence

ORD record
ord-5a6c318792ed478a99368ec13a2263ab
Source dataset
uspto-grants-1981_12
Patent number
US04304770

Reaction notes

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