Diisopropyl Ether → HCID 178480384, compound

HRID 1088061Notes

Reaction equation

HRID 1088061 reaction equation
C[N+](C)=CCl.[Cl-].P(Cl)(Cl)(Cl)=O.Cl[CH2:13][C:14](=O)[C:15](=[N:19][O:20][CH:21]([F:23])[F:22])[C:16]([OH:18])=O.[NH2:25][C@@H:26]1[C:43](=[O:44])[N:28]2[C:29]([C:40]([O-:42])=[O:41])=[C:30]([CH2:33][N+:34]3[N:35]([CH3:39])[CH:36]=[CH:37][CH:38]=3)[CH2:31][S:32][C@H:27]12.C[Si](C)(C)NC(=O)C.[NH2:53][C:54]([NH2:56])=[S:55].C(OC(C)C)(C)C>O1CCCC1.CN(C)C(=O)C.CCCCCC.CN(C)C=O>[NH2:56][C:54]1[S:55][CH:13]=[C:14]([C:15](=[N:19][O:20][CH:21]([F:23])[F:22])[C:16]([NH:25][C@@H:26]2[C:43](=[O:44])[N:28]3[C:29]([C:40]([O-:42])=[O:41])=[C:30]([CH2:33][N+:34]4[N:35]([CH3:39])[CH:36]=[CH:37][CH:38]=4)[CH2:31][S:32][C@H:27]23)=[O:18])[N:53]=1

Participants

12

Reactant 7

HCID 7914Diisopropyl EtherHCID 24813Phosphorus oxychlorideHCID 25989Acetamide, N-(trimethylsilyl)-HCID 77311Chloro-N,N-dimethylformiminium chlorideHCID 2723790ThioureaHCID 539879194-Chloro-2-difluoromethoxyimino-3-oxobutyric acidHCID 178480378HCID 178480378, compound

Product 1

HCID 178480384HCID 178480384, compoundYield 26.2%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 31374DimethylacetamideSolvent

Procedure

To a suspension of Vilsmeier reagent prepared from N,N-dimethylformamide (0.158 ml) and phosphoryl chloride (0.187 ml) in tetrahydrofuran (1 ml) was added a solution of 4-chloro-2-difluoromethoxyimino-3-oxobutyric acid (0.4 g) in tetrahydrofuran (4 ml) under ice-cooling with stirring. After stirred at the same temperature for 30 minutes, this activated acid solution was added to a solution of bis(trifluoroacetic acid) salt of 7β-amino-3-(2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate (0.80 g) and N-(trimethylsilyl)acetamide (2.9 g) in tetrahydrofuran (20 ml) under ice-cooling. The mixture was stirred at the same temperature for 1.5 hours. To the resultant mixture was added a solution of thiourea (230 mg) in N,N-dimethylacetamide (2.3 ml) at ambient temperature. After stirred at 30°-35° C. for 4 hours, the resultant solution was poured into a mixture of n-hexane (30 ml) and diisopropyl ether (50 ml). The precipitated mass was triturated in ethyl acetate and dried under reduced pressure. The dried glassy mass was dissolved in water (20 ml) and the aqueous solution was washed with ethyl acetate twice, adjusted to pH 2.0 with 5% aqueous sodium bicarbonate solution, and subjected to column chromatography on macroporous nonionic adsorption resin "Diaion HP-20". The column was washed with water and the object compound was eluted with 30% aqueous methanol. The fraction containing the object compound was concentrated under reduced pressure and the residue was lyophilized to give 7β-[2-(2-aminothiazol-4-yl)-2-(difluoromethoxyimino)acetamido]-3-(2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate (syn isomer) (0.25 g).

Workup

  1. temperaturecooling
  2. stirringAfter stirred at the same temperature for 30 minutes
  3. temperaturecooling
  4. stirringThe mixture was stirred at the same temperature for 1.5 hours
  5. stirringAfter stirred at 30°-35° C. for 4 hours
  6. customThe precipitated mass was triturated in ethyl acetate
  7. customdried under reduced pressure
  8. dissolutionThe dried glassy mass was dissolved in water (20 ml)
  9. washthe aqueous solution was washed with ethyl acetate twice
  10. washThe column was washed with water
  11. washthe object compound was eluted with 30% aqueous methanol
  12. additionThe fraction containing the object compound
  13. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-5c9fb46333424f21a44d42a2d55dd86a
Source dataset
uspto-grants-1990_10
Patent number
US04960766

Reaction notes

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