Sodium Chloride → HCID 131712612, compound

HRID 1659845Notes

Reaction equation

HRID 1659845 reaction equation
P(Cl)(Cl)(Cl)=O.[CH2:6]([O:9][N:10]=[C:11]([C:15]1[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=1)[C:12]([OH:14])=O)[C:7]#[CH:8].[CH3:23][CH:24]1[CH:29]=[C:28]([C:30]([OH:32])=[O:31])[N:27]2[C:33](=[O:36])[CH:34]([NH2:35])[C@H:26]2[S:25]1.C[Si](CC(N)=O)(C)C.[Cl-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)(=O)C.O1CCCC1.CN(C)C=O>[CH3:23][CH:24]1[CH:29]=[C:28]([C:30]([OH:32])=[O:31])[N:27]2[C:33](=[O:36])[CH:34]([NH:35][C:12](=[O:14])[C:11](=[N:10][O:9][CH2:6][C:7]#[CH:8])[C:15]3[N:16]=[C:17]([NH:20][CH:21]=[O:22])[S:18][CH:19]=3)[C@H:26]2[S:25]1

Participants

10

Reactant 6

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 128022512-Methyl-7-amino-3-cephem-4-carboxylic acidHCID 537194582-(2-Formamidothiazol-4-yl)-2-(propargyloxyimino)acetic acid

Product 1

HCID 131712612HCID 131712612, compoundYield 97.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-25 °C

Procedure

To dimethylformamide (0.4 g) was added dropwise phosphorus oxychloride (0.84 g) under stirring and ice-cooling, and the mixture was stirred for 30 minutes at 40° C. and then suspended in ethyl acetate (10 ml). To the suspension was added 2-(2-propynyloxyimino)-2-(2-formylaminothiazol-4-yl)acetic acid (syn isomer) (1.27 g) under stirring and ice-cooling and then stirred for 30 minutes under ice-cooling. Thus obtained solution was added to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (1.44 g) and trimethylsilylacetamide (5.2 g) in tetrahydrofuran (40 ml), under cooling to -25° C. The mixture was stirred for 1 hour at -20° C. to -10° C., and a saturated aqueous solution of sodium chloride (100 ml) was added thereto. Thus obtained mixture was adjusted to pH 7.5 with 20% aqueous solution of sodium carbonate, and the aqueous layer was separated. To the aqueous layer was added ethyl acetate, and adjusted to pH 2 with 10% hydrochloric acid, and then extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and then evaporated. The residue was pulverized in diethyl ether, collected by filtration and then dried to give 2-methyl-7-[2-(2-propynyloxyimino)-2-(2-formylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid (syn isomer) (2.2 g).

Workup

  1. temperatureice-cooling
  2. stirringthe mixture was stirred for 30 minutes at 40° C.
  3. stirringunder stirring
  4. temperatureice-cooling
  5. stirringstirred for 30 minutes under ice-
  6. temperaturecooling
  7. additionThus obtained solution was added to a solution, which
  8. customwas prepared
  9. stirringby stirring
  10. stirringThe mixture was stirred for 1 hour at -20° C. to -10° C.
  11. customthe aqueous layer was separated
  12. additionTo the aqueous layer was added ethyl acetate
  13. extractionextracted with ethyl acetate
  14. washThe ethyl acetate layer was washed with a saturated aqueous solution of sodium chloride
  15. dry with materialdried over magnesium sulfate
  16. customevaporated
  17. filtrationcollected by filtration
  18. customdried

Sources & evidence

ORD record
ord-6a56a5dea20f4912aeb72b16a0b7b99d
Source dataset
uspto-grants-1981_12
Patent number
US04305937

Reaction notes

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