Phosphorus oxychloride → HCID 131712731, compound

HRID 1388478Notes

Reaction equation

HRID 1388478 reaction equation
[CH2:1]([O:4][N:5]=[C:6]([C:10]1[N:11]=[C:12]([NH2:15])[S:13][CH:14]=1)[C:7]([OH:9])=O)[CH:2]=[CH2:3].P(Cl)(Cl)(Cl)=O.C[Si](CC(N)=O)(C)C.[NH2:29][CH:30]1[C:47](=[O:48])[N:32]2[C:33]([C:44]([OH:46])=[O:45])=[C:34]([CH2:37][S:38][C:39]3[S:40][CH:41]=[N:42][N:43]=3)[CH2:35][S:36][C@H:31]12>O1CCCC1.C(=O)(O)[O-].[Na+].O.CC(C)=O.CN(C)C=O>[CH2:1]([O:4][N:5]=[C:6]([C:10]1[N:11]=[C:12]([NH2:15])[S:13][CH:14]=1)[C:7]([NH:29][CH:30]1[C:47](=[O:48])[N:32]2[C:33]([C:44]([OH:46])=[O:45])=[C:34]([CH2:37][S:38][C:39]3[S:40][CH:41]=[N:42][N:43]=3)[CH2:35][S:36][C@H:31]12)=[O:9])[CH:2]=[CH2:3]

Participants

10

Reactant 4

HCID 24813Phosphorus oxychloride2×HCID 357676Acetamide, 2-(trimethylsilyl)-HCID 128891877-Amino-3-(1,3,4-thiadiazol-2-ylthiomethyl)-3cephem-4-carboxylic acidHCID 544842532-(2-Aminothiazol-4-yl)-2-allyloxyiminoacetic acid

Product 1

HCID 131712731HCID 131712731, compoundYield 63.3%

Reagents, catalysts & solvents 5

HCID 180AcetoneSolventHCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

Water (0.05 g) was added to a suspension of 2-allyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetic acid (syn isomer)(1.0 g) in tetrahydrofuran (10 ml). Phosphorus oxychloride (0.84 g) was added thereto at 0° to 5° C. and the mixture was stirred for 20 minutes at the same temperature. Trimethylsilylacetamide (0.66 g) was added thereto, the mixture was stirred for 20 minutes at the same temperature, phosphorus oxychloride (0.84 g) was added thereto, the resulting mixture was stirred for 20 minutes at 0° to 5° C., dimethylformamide (0.45 g) was added thereto and the resulting mixture was stirred for 1 hour at the same temperature. The resulting solution was added dropwise at -5° to 5° C. and pH 7.0 to 8.0 to a solution, which was prepared by adding acetone (15 ml) and tetrahydrofuran (15 ml) to a solution of 7-amino-3-(1,3,4-thiadiazol- 2-yl)thiomethyl-3-cephem-4-carboxylic acid (1.45 g) in a mixture of sodium bicarbonate (0.42 g) and water (10 ml). The resulting mixture was stirred for 2 hours under ice-cooling keeping the pH of the mixture at 7.0 to 8.0 and then adjusted to pH 7.5. An insoluble material was filtered off and the filtrate was washed with ethyl acetate. The aqueous layer was adjusted to pH 6.0 and organic solvent in the aqueous layer was distilled off under reduced pressure. The remaining aqueous layer was adjusted to pH 4.0 and an insoluble material was filtered off. The filtrate was adjusted to pH 3.0 and precipitates were collected by filtration and dried to give 7-[2-allyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer) (1.5 g).

Workup

  1. additionwas added
  2. stirringthe resulting mixture was stirred for 20 minutes at 0° to 5° C.
  3. stirringthe resulting mixture was stirred for 1 hour at the same temperature
  4. additionThe resulting solution was added dropwise at -5° to 5° C.
  5. custompH 7.0 to 8.0 to a solution, which was prepared
  6. stirringThe resulting mixture was stirred for 2 hours under ice-
  7. temperaturecooling
  8. filtrationAn insoluble material was filtered off
  9. washthe filtrate was washed with ethyl acetate
  10. distillationwas distilled off under reduced pressure
  11. filtrationan insoluble material was filtered off
  12. customprecipitates
  13. filtrationwere collected by filtration
  14. customdried

Sources & evidence

ORD record
ord-63cce9d6ef754c5cbfd93edbb1822bf7
Source dataset
uspto-grants-1984_02
Patent number
US04431643

Reaction notes

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