Trifluoromethanesulfonic acid → t-Butyl 3-acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylate

HRID 464482Notes

Reaction equation

HRID 464482 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:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])(=[O:3])[CH3:2].C(O[CH:26](OCC)[CH2:27][N:28]=[C:29]=[N:30][Si](C(C)(C)C)(C)C)C.FC(F)(F)S(O)(=O)=O>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:29]3[NH:28][CH:27]=[CH:26][N:30]=3)[C:19](=[O:22])[N:10]2[C:11]=1[C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 62406Trifluoromethanesulfonic acidHCID 15573429t-Butyl 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylateHCID 202633371-(2,2-Diethoxyethyl)-3-t-butyldimethylsilylcarbodiimide

Product 1

HCID 70445914t-Butyl 3-acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of t-butyl 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylate (3.3 g.) and 1-(2,2-diethoxyethyl)-3-t-butyldimethylsilylcarbodiimide (2.0 g.) in CH2Cl2 (50 ml.) at room temperature was added trifluoromethanesulphonic acid (0.89 ml.) over 2 minutes. The mixture was evaporated to dryness and the residue, t-butyl 3-acetoxymethyl-7-[2-(2,2-diethoxyethyl)-3-t-butyldimethylsilyl]guanidinoceph-3-em-4-carboxylate, was dissolved in acetonitrile (50 ml.) and the mixture treated first with 50% w/v aqueous HF (0.8 ml.) at room temperature for 15 minutes and then with 12N aqueous HCl (1.0 ml.) for 1.5 hours at room temperature. The reaction mixture was evaporated to dryness and the residue triturated with ether to give t-butyl 3-acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylate as a mixture of salts. This powder was dissolved in TFA (5 ml.) and this solution allowed to stand for 15 minutes at room temperature. The solvent was evaporated and the residue triturated with ether (yield from 7-amino derivative 41%) and then purified by chromatography on "Dowex" 1 resin (acetate form) using 0.1% v/v aqueous HOAc as eluant to give 3-acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylic acid (yield from 7-amino derivaive 34%) having the following n.m.r. in d6DMSO: 2.1 (s, 3H); 3.45 (d, 1H); 3.7 (d, 1H); 4.8 (d, 1H); 5.15 (d, 1H); 5.3 (d, 1H); 5.7 (d, 1H); 7.1 (s, 2H); 9.4 (d, 1H).

Workup

  1. customThe mixture was evaporated to dryness
  2. dissolutionthe residue, t-butyl 3-acetoxymethyl-7-[2-(2,2-diethoxyethyl)-3-t-butyldimethylsilyl]guanidinoceph-3-em-4-carboxylate, was dissolved in acetonitrile (50 ml.)
  3. additionthe mixture treated first with 50% w/v aqueous HF (0.8 ml.) at room temperature for 15 minutes
  4. customThe reaction mixture was evaporated to dryness
  5. customthe residue triturated with ether

Sources & evidence

ORD record
ord-4b592b0c3b5149f18526ae4d2dac37c6
Source dataset
uspto-grants-1985_10
Patent number
US04547573

Reaction notes

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