p-Toluenesulfonic acid → 3-Acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylic acid

HRID 464483Notes

Reaction equation

HRID 464483 reaction equation
[C:1]([O:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:20]([NH2:21])[C:19](=[O:22])[N:10]2[C:11]=1[C:12]([O:14]C(C)(C)C)=[O:13])(=[O:3])[CH3:2].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(O[CH:37](OCC)[CH2:38][N:39]=[C:40]=[N:41][Si](C)(C)C)C>C(Cl)Cl>[C:1]([O:4][CH2:5][C:6]1[CH2:7][S:8][C@@H:9]2[CH:20]([NH:21][C:40]3[NH:39][CH:38]=[CH:37][N:41]=3)[C:19](=[O:22])[N:10]2[C:11]=1[C:12]([OH:14])=[O:13])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 135569311-(2,2-Diethoxyethyl)-3-trimethylsilylcarbodiimideHCID 15573429t-Butyl 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylate

Product 1

HCID 704454913-Acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylic acidYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of t-butyl 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylate (164 mg.) in anhydrous CH2Cl2 at room temperature was added a molar solution of anhydrous toluene-p-sulphonic acid in CH2Cl2 (0.5 ml.) and then 1-(2,2-diethoxyethyl)-3-trimethylsilylcarbodiimide (125 μl.). Stirring was continued for 10 minutes and the solvent was evaporated. The residue, t-butyl 3-acetoxymethyl-7-[2-(2,2-diethoxyethyl)-3-trimethylsilyl]guanidinoceph-3-em-4-carboxylate, was dissolved in acetonitrile and 12N aqueous HCl (42 μl.) added. The mixture was stirred for 1.5 hours at room temperature, and the solvent evaporated. To the residue, t-butyl 3-acetoxymethyl-7-(imidazol-2 -yl)aminoceph-3-em-4-carboxylate, was added trifluoracetic acid and the mixture was stirred for 15 minutes. The solvent was evaporated and the residue was precipitated from a solution in the minimum of CH2Cl2 with ether. The precipitate was dissolved in CH2Cl2 /MeOH and the solvent evaporated to give 3-acetoxymethyl- 7-(imidazol-2-yl)aminoceph-3-em-4-carboxylic acid (262 mg. of 42% strength), identical with the product obtained in Example 2 (yield from 7-amino derivative 65%).

Workup

  1. customthe solvent was evaporated
  2. dissolutionThe residue, t-butyl 3-acetoxymethyl-7-[2-(2,2-diethoxyethyl)-3-trimethylsilyl]guanidinoceph-3-em-4-carboxylate, was dissolved in acetonitrile
  3. addition12N aqueous HCl (42 μl.) added
  4. stirringThe mixture was stirred for 1.5 hours at room temperature
  5. customthe solvent evaporated
  6. additionTo the residue, t-butyl 3-acetoxymethyl-7-(imidazol-2 -yl)aminoceph-3-em-4-carboxylate, was added trifluoracetic acid
  7. stirringthe mixture was stirred for 15 minutes
  8. customThe solvent was evaporated
  9. customthe residue was precipitated from a solution in the minimum of CH2Cl2 with ether
  10. dissolutionThe precipitate was dissolved in CH2Cl2 /MeOH
  11. customthe solvent evaporated

Sources & evidence

ORD record
ord-6d6dbabed3ba4a57a501a0a719a76ef3
Source dataset
uspto-grants-1985_10
Patent number
US04547573

Reaction notes

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