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

HRID 1463167Notes

Reaction equation

HRID 1463167 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:12]([O:15][CH2:16][C:17]1[CH2:18][S:19][C@@H:20]2[CH:27]([NH2:28])[C:26](=[O:29])[N:21]2[C:22]=1[C:23]([OH:25])=[O:24])(=[O:14])[CH3:13].F[C:31]1[NH:32][CH:33]=[CH:34][N:35]=1>CN(C=O)C>[C:12]([O:15][CH2:16][C:17]1[CH2:18][S:19][C@@H:20]2[CH:27]([NH:28][C:31]3[NH:32][CH:33]=[CH:34][N:35]=3)[C:26](=[O:29])[N:21]2[C:22]=1[C:23]([OH:25])=[O:24])(=[O:14])[CH3:13]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 5595422-Fluoro-1H-imidazoleHCID 113463103-Acetoxymethyl-7-amino-3cephem-4-carboxylic acid

Product 1

HCID 704454913-Acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylic acidYield 28.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of anhydrous toluene-p-sulphonic acid (0.74 g.) and 3-acetoxymethyl-7-aminoceph-3-em-4-carboxylic acid (1.17 g.) in dry DMF (17.5 ml.) was stirred for 15 minutes at room temperature to effect partial solution. One portion of 2-fluoroimidazole (0.74 g.) was then added and the mixture stirred at 90° for 2 hours. The solvent was evaporated at ambient temperature, 2% v/v aqueous HOAc (20 ml.) was added to the residue and the mixture was extracted with EtOAc (20 ml.). The aqueous layer was concentrated to 15 ml., filtered and the filtrate purified by preparative HPLC on Whatman "Partisil 10" using water/MeOH/HOAc 80:20:1 v/v/v as solvent. The product was further purified by trituration with acetone and washing with acetone and ether to give 3-acetoxymethyl-7-(imidazol-2-yl)aminoceph-3-em-4-carboxylic acid (0.42 g.) as a hydrated mixed acetate/toluene-p-sulphonate salt having m.p. >160° (decomp.) and the following n.m.r. in D2O: 2.28 (s, 3H); 3.58 (d, 1H); 3.89 (d, 1H); 4.92 (d, 1H); 5.13 (d, 1H); 5.42 (d, 1H); 5.70 (d, 1H); 7.08 (s, 2H).

Workup

  1. stirringthe mixture stirred at 90° for 2 hours
  2. customThe solvent was evaporated at ambient temperature
  3. addition2% v/v aqueous HOAc (20 ml.) was added to the residue
  4. extractionthe mixture was extracted with EtOAc (20 ml.)
  5. concentrationThe aqueous layer was concentrated to 15 ml
  6. filtration, filtered
  7. customthe filtrate purified by preparative HPLC on Whatman "Partisil 10"
  8. customThe product was further purified by trituration with acetone
  9. washwashing with acetone and ether

Sources & evidence

ORD record
ord-3a6bff0d8bef4b10aadc620caf7ac68a
Source dataset
uspto-grants-1984_07
Patent number
US04463173

Reaction notes

Loading…