Thionyl Chloride → 2-Methyl-7-[2-(2-formylaminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid

HRID 1701133Notes

Reaction equation

HRID 1701133 reaction equation
S(Cl)(Cl)=O.[CH:5]([NH:7][C:8]1[S:9][CH:10]=[C:11]([C:13](=[O:17])[C:14]([OH:16])=O)[N:12]=1)=[O:6].[CH3:18][CH:19]1[CH:24]=[C:23]([C:25]([OH:27])=[O:26])[N:22]2[C:28](=[O:31])[CH:29]([NH2:30])[C@H:21]2[S:20]1.C[Si](CC(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.CN(C)C=O>[CH3:18][CH:19]1[CH:24]=[C:23]([C:25]([OH:27])=[O:26])[N:22]2[C:28](=[O:31])[CH:29]([NH:30][C:14](=[O:16])[C:13]([C:11]3[N:12]=[C:8]([NH:7][CH:5]=[O:6])[S:9][CH:10]=3)=[O:17])[C@H:21]2[S:20]1

Participants

10

Reactant 6

HCID 24386Thionyl ChlorideHCID 357676Acetamide, 2-(trimethylsilyl)-HCID 516892Sodium BicarbonateHCID 128022512-Methyl-7-amino-3-cephem-4-carboxylic acidHCID 13116693(2-Formamido-1,3-thiazol-4-yl)(oxo)acetic acidHCID 178522624HCID 178522624, compound

Product 1

HCID 1317114932-Methyl-7-[2-(2-formylaminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of thionyl chloride (3.01 g.) in methylene chloride (45 ml.) were added dimethylformamide (0.928 g.) and 2-(2-formylaminothiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylic acid, (3.71 g.) in turn, and the mixture was stirred for 4 hours at room temperature. Thus obtained mixture was added over 5 minutes to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (3.3 g.) and trimethylsilylacetamide (16.2 g.) in methylene chloride (60 ml.) at room temperature for 40 minutes, with stirring under cooling to -25° to -20° C. The mixture was stirred for 30 minutes at -25° to -20° C., for 30 minutes at -10° to 0° C., and then for 30 minutes at room temperature. To the reaction mixture was added water (30 ml.), and the mixture was stirred for 10 minutes. After a saturated aqueous sodium bicarbonate solution was added to the mixture in order to dissolve the precipitates, the aqueous layer was separated. To the aqueous layer was added ethyl acetate, and the mixture was adjusted to pH 2 with 2 N hydrochloric acid, and then the ethyl acetate layer was separated. The remaining aqueous layer was further extracted with ethyl acetate. The ethyl acetate layers were combined together, washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate and then concentrated. Thus obtained crystalline residue was pulverized in diethyl ether, collected by filtration and then dried to give yellow crystalline powder of 2-methyl-7-[2-(2-formylaminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, which can be represented as 2-methyl-7-[2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, (3.81 g.).

Workup

  1. additionThus obtained mixture was added over 5 minutes to a solution, which
  2. customwas prepared
  3. stirringby stirring
  4. stirringwith stirring
  5. temperatureunder cooling to -25° to -20° C
  6. stirringThe mixture was stirred for 30 minutes at -25° to -20° C., for 30 minutes at -10° to 0° C.
  7. waitfor 30 minutes at room temperature
  8. stirringthe mixture was stirred for 10 minutes
  9. dissolutionto dissolve the precipitates
  10. customthe aqueous layer was separated
  11. additionTo the aqueous layer was added ethyl acetate
  12. customthe ethyl acetate layer was separated
  13. extractionThe remaining aqueous layer was further extracted with ethyl acetate
  14. washwashed with a saturated aqueous sodium chloride solution
  15. dry with materialdried over magnesium sulfate
  16. concentrationconcentrated
  17. filtrationcollected by filtration
  18. customdried

Sources & evidence

ORD record
ord-46b710dc94764847adbc3ae0c85c8709
Source dataset
uspto-grants-1980_03
Patent number
US04191762

Reaction notes

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