Hydrochloric Acid → (6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 1700796Notes

Reaction equation

HRID 1700796 reaction equation
[NH2:1][CH:2]1[C:14](=[O:15])[N:4]2[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]12.[NH2:16][C:17]1[S:18][CH:19]=[C:20](/[C:22](=[N:26]/[O:27]C(=O)C)/[C:23](Cl)=[O:24])[N:21]=1.Cl.C([O-])(O)=O.[Na+].C([O-])([O-])=O.[K+].[K+].S(=O)(=O)(O)O>ClCCl.O>[NH2:16][C:17]1[S:18][CH:19]=[C:20](/[C:22](=[N:26]/[OH:27])/[C:23]([NH:1][CH:2]2[C:14](=[O:15])[N:4]3[C:5]([C:11]([OH:13])=[O:12])=[C:6]([CH:9]=[CH2:10])[CH2:7][S:8][C@H:3]23)=[O:24])[N:21]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 1118Sulfuric AcidHCID 11430Potassium CarbonateHCID 516892Sodium Bicarbonate2×HCID 11322595[(Z)-[1-(2-amino-1,3-thiazol-4-yl)-2-chloro-2-oxoethylidene]amino] acetateHCID 128180067-Amino-3vinyl-3-cephem-4-carboxylic acid

Product 1

HCID 13336170(6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

40 g of 7-amino-3-vinyl-3-cephem-4-carboxylic acid in 400 ml of dichloromethane are treated with 55.7 ml of N,O-bistnmethyl-silylacetamid. The mixture obtained is stirred for ca. 2 hours at room temperature, cooled to 0° and treated with 52.2 g of 2-(Z)-(2-aminothiazol-4-yl) -2-acetoxyiminoacetic acid chloride in the form of a hydrochloride in small portions. The mixture obtained is stirred for ca.90 minutes at 0° and added under stirring to a mixture of 44.55 g of NaHCO3, 600 ml of water und 100 ml of dichloromethane of a temperature of 5°. The pH of the mixture obtained is adjusted to a pH of ca. 7.2-7.3 with a saturated aqueous solution of NaHCO3. The phases formed are separated. To the aqueous phase 300 ml of water are added and 28.7 g of NH4Cl. The pH of the mixture obtained is adjusted to pH 8 by addition of an aqueous 10% K2CO3 solution and the mixture is stirred for ca. 80 minutes. A solution is obtained. The pH of the solution obtained is adjusted to pH 3 by addition of 5 m sulphuric acid. 7-(Z)-[2-(2-amino-thiazol4-yl)-2-hydroxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylic acid precipitates, is filtrated off, washed with water and dried. 7-(Z)-[2-(2-amino-thiazol-4-yl)-2-hydroxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylic acid in a purity of 94.3 % is obtained.

Workup

  1. customThe mixture obtained
  2. temperaturecooled to 0°
  3. customThe mixture obtained
  4. stirringis stirred for ca
  5. addition90 minutes at 0° and added
  6. customThe pH of the mixture obtained
  7. customThe phases formed
  8. customare separated
  9. additionTo the aqueous phase 300 ml of water are added
  10. customThe pH of the mixture obtained
  11. stirringthe mixture is stirred for ca. 80 minutes
  12. customA solution is obtained
  13. customThe pH of the solution obtained
  14. custom7-(Z)-[2-(2-amino-thiazol4-yl)-2-hydroxyiminoacetamido]-3-vinyl-3-cephem-4-carboxylic acid precipitates
  15. filtrationis filtrated off
  16. washwashed with water
  17. customdried

Sources & evidence

ORD record
ord-cc4cf69fc2314f6a9127aef995f58ee4
Source dataset
uspto-grants-2002_02
Patent number
US06350869B1

Reaction notes

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