Hydrochloric Acid → benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 992710Notes

Reaction equation

HRID 992710 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:43]/[O:44]C(=O)C)/[C:8]([NH:10][C@@H:11]2[C:41](=[O:42])[N:13]3[C:14]([C:25]([O:27][CH:28]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])=[C:15]([S:18][CH2:19][C:20]4[CH:21]=[N:22][NH:23][CH:24]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.Cl.[OH-].[Na+].[OH-].[K+]>CO.C(OCC)(=O)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:43]/[OH:44])/[C:8]([NH:10][C@@H:11]2[C:41](=[O:42])[N:13]3[C:14]([C:25]([O:27][CH:28]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)=[O:26])=[C:15]([S:18][CH2:19][C:20]4[CH:21]=[N:22][NH:23][CH:24]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 88158439benzhydryl (6R,7R)-7-[[(2Z)-2-acetyloxyimino-2-(2-amino-1,3-thiazol-4-yl)acetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 88157260benzhydryl (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 86.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (41.3 g) was suspended in methanol (420 ml) at room temperature, concentrated hydrochloric acid (24.9 ml) was added below 15° C. thereto. After the reaction mixture was stirred at room temperature for 30 minutes, concentrated hydrochloric acid (6.7 ml) was added thereto at the same temperature. After stirring at room temperature for 2 hours, poured into a mixture of ethyl acetate (1.2 l) and pH 6.86 buffer (1.5 l). The pH was adjusted to pH 5.0 with 30% aqueous sodium hydroxide, and then was adjusted to pH 6.0 with 2N-potassium hydroxide. The organic layer was separated, and herein THF (0.5 l) was added thereto with brine (1.0 l). The organic layer was washed with brine (1.0 l), dried over magnesium sulfate, and evaporated until the volume amounted to 500 ml. A mixture of IPE (500 ml) and ethyl acetate (700 ml) was added thereto. Resulting precipitate was filtered, dried under reduced pressure to afford diphenylmethyl 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylate (33.6 g) as powder.

Workup

  1. stirringAfter stirring at room temperature for 2 hours
  2. customThe organic layer was separated
  3. additionherein THF (0.5 l) was added
  4. washThe organic layer was washed with brine (1.0 l)
  5. dry with materialdried over magnesium sulfate
  6. customevaporated until the volume
  7. additionA mixture of IPE (500 ml) and ethyl acetate (700 ml)
  8. additionwas added
  9. customResulting precipitate
  10. filtrationwas filtered
  11. customdried under reduced pressure

Sources & evidence

ORD record
ord-c1785b6bb5ca429ea9b1fa49dd4fd6b5
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

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