Hydrochloric Acid → 2-Methyl-7-[2-hydroxy-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid hydrochloride

HRID 1701135Notes

Reaction equation

HRID 1701135 reaction equation
[ClH:1].[CH3:2][CH:3]1[CH:8]=[C:7]([C:9]([OH:11])=[O:10])[N:6]2[C:12](=[O:25])[CH:13]([NH:14][C:15](=[O:24])[C:16]([C:18]3[N:19]=[C:20]([NH2:23])[S:21][CH:22]=3)=[O:17])[C@H:5]2[S:4]1.[OH-].[Na+].[BH4-].[Na+].Cl>CO>[ClH:1].[CH3:2][CH:3]1[CH:8]=[C:7]([C:9]([OH:11])=[O:10])[N:6]2[C:12](=[O:25])[CH:13]([NH:14][C:15](=[O:24])[CH:16]([OH:17])[C:18]3[N:19]=[C:20]([NH2:23])[S:21][CH:22]=3)[C@H:5]2[S:4]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 1317117222-Methyl-7-[2-(2-aminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid hydrochlorideHCID 178427250HCID 178427250, compound

Product 1

HCID 705897632-Methyl-7-[2-hydroxy-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Procedure

To a suspension of 2-methyl-7-[2-(2-aminothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid hydrochloride, which can be represented as 2-methyl-7-[2-(2-imino-2,3-dihydrothiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid hydrochloride, (3.80 g.) in methanol (70 ml.) was added 1 N sodium hydroxide aqueous solution (18.8 ml.) under ice-cooling and stirring. To the mixture was added sodium borohydride (0.13 g.) over 20 minutes under ice-cooling and stirring and the mixture was stirred for 30 minutes at the same temperature. After the reaction, methanol was distilled off from the reaction mixture. To the residue was added cold water (60 ml.), and the mixture was washed with ethyl acetate, adjusted to pH 2 with 10% hydrochloric acid and then filtered. The filtrate was subjected to column chromatography (non-ionic adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries) and the column was washed with water and then eluted with 10% aqueous isopropyl alcohol solution. The eluates containing the object compound were collected and then lyophilized to produce pale yellow powder. (1.80 g.). To the powder were added methanol (10 ml.) and 35% hydrochloric acid (0.5 g.) in turn, and thus obtained solution was subjected to column chromatography using activated carbon (2.0 g.) and then the column was eluted with methanol. The eluates containing the object compound were collected and then the solvent was distilled off under reduced pressure. The residue was washed with ethyl acetate and then dried to give 2-methyl-7-[2-hydroxy-2-(2-aminothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid hydrochloride, which can be represented as 2-methyl-7-[2-hydroxy-2-(2-imino-2,3-dihydrothiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid hydrochloride, (1.10 g.), mp >250° C.

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. stirringstirring
  4. stirringthe mixture was stirred for 30 minutes at the same temperature
  5. distillationwas distilled off from the reaction mixture
  6. additionTo the residue was added cold water (60 ml.)
  7. washthe mixture was washed with ethyl acetate
  8. filtrationfiltered
  9. customThe filtrate was subjected to column chromatography (non-ionic adsorption resin, Diaion HP 20 prepared by Mitsubishi Chemical Industries)
  10. washthe column was washed with water
  11. washeluted with 10% aqueous isopropyl alcohol solution
  12. additionThe eluates containing the object compound
  13. customwere collected
  14. customto produce pale yellow powder
  15. washthe column was eluted with methanol
  16. additionThe eluates containing the object compound
  17. customwere collected
  18. distillationthe solvent was distilled off under reduced pressure
  19. washThe residue was washed with ethyl acetate
  20. customdried

Sources & evidence

ORD record
ord-d4a7a42e3b264534afc6e257990ccb6a
Source dataset
uspto-grants-1980_03
Patent number
US04191762

Reaction notes

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