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

HRID 1155156Notes

Reaction equation

HRID 1155156 reaction equation
P(Cl)(Cl)(Cl)=O.[CH:6]([NH:8][C:9]1[S:10][CH:11]=[C:12]([C:14](=[O:18])[C:15]([OH:17])=O)[N:13]=1)=[O:7].[CH3:19][CH:20]1[CH:25]=[C:24]([C:26]([OH:28])=[O:27])[N:23]2[C:29](=[O:32])[CH:30]([NH2:31])[C@H:22]2[S:21]1.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.CN(C)C=O>[CH3:19][CH:20]1[CH:25]=[C:24]([C:26]([OH:28])=[O:27])[N:23]2[C:29](=[O:32])[CH:30]([NH:31][C:15](=[O:17])[C:14]([C:12]3[N:13]=[C:9]([NH:8][CH:6]=[O:7])[S:10][CH:11]=3)=[O:18])[C@H:22]2[S:21]1

Participants

10

Reactant 6

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 11708267BistrimethylsilylacetamidHCID 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 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

Procedure

To dimethylformamide (78 ml.) was added dropwise phosphorus oxychloride (11.9 g.) under stirring and icecooling, and the mixture was stirred for 30 minutes at 40° C. To the mixture was added 2-(2-formylaminothiazol-4-yl)glyoxylic acid, which can be represented as 2-(2-formylimino-2,3-dihydrothiazol-4-yl)glyoxylic acid, (7.8 g.) under cooling at -20° C., and then the mixture was stirred for 30 minutes under cooling at -20° to -15° C. Thus obtained mixture was added to a solution, which was prepared by stirring a mixture of 2-methyl-7-amino-3-cephem-4-carboxylic acid (8.35 g.) and bis(trimethylsilyl)acetamide (19.5 ml.) in dried methylene chloride (170 ml.) at room temperature, under cooling at -50° to -45° C. with stirring. The mixture was stirred for 1 hour at -45° to -40° C. and then the reaction mixture was poured into a solution of sodium bicarbonate (32 g.) in water (1.5 l) with shaking. The aqueous layer was separated and washed with ethyl acetate. The aqueous solution was layered with ethyl acetate and then adjusted to pH 1 to 2 with concentrated hydrochloric acid. The ethyl acetate layer was separated from the mixture, and the remaining aqueous layer was extracted with ethyl acetate (200 ml.×2). The ethyl acetate layers were combined together, washed with water and then concentrated to a small volume. The precipitates were collected by filtration, washed with a small amount of ethyl acetate and then dried to give 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, (7.9 g.), mp 210° to 215° C. (dec.).

Workup

  1. stirringthe mixture was stirred for 30 minutes at 40° C
  2. stirringthe mixture was stirred for 30 minutes
  3. temperatureunder cooling at -20° to -15° C
  4. additionThus obtained mixture was added to a solution, which
  5. customwas prepared
  6. stirringby stirring
  7. temperatureunder cooling at -50° to -45° C.
  8. stirringwith stirring
  9. stirringThe mixture was stirred for 1 hour at -45° to -40° C.
  10. stirringwith shaking
  11. customThe aqueous layer was separated
  12. washwashed with ethyl acetate
  13. customThe ethyl acetate layer was separated from the mixture
  14. extractionthe remaining aqueous layer was extracted with ethyl acetate (200 ml.×2)
  15. washwashed with water
  16. concentrationconcentrated to a small volume
  17. filtrationThe precipitates were collected by filtration
  18. washwashed with a small amount of ethyl acetate
  19. customdried

Sources & evidence

ORD record
ord-0fc41ac96ac248fdb700020134ef6a07
Source dataset
uspto-grants-1981_11
Patent number
US04299829

Reaction notes

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