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

HRID 2412470Notes

Reaction equation

HRID 2412470 reaction equation
C([C:4]1[N:5]=[C:6](F)[N:7]([C:9]([C:22]2[CH:27]=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:8]=1)C=C.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[C:41]([O:44][CH2:45][C:46]1[CH2:47][S:48][C@@H:49]2[CH:56]([NH2:57])[C:55](=[O:58])[N:50]2[C:51]=1[C:52]([OH:54])=[O:53])(=[O:43])[CH3:42]>CN(C=O)C>[C:41]([O:44][CH2:45][C:46]1[CH2:47][S:48][C@@H:49]2[CH:56]([NH:57][C:6]3[N:7]([CH2:9][CH:22]=[CH2:27])[CH:8]=[CH:4][N:5]=3)[C:55](=[O:58])[N:50]2[C:51]=1[C:52]([OH:54])=[O:53])(=[O:43])[CH3:42]

Participants

5

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 113463103-Acetoxymethyl-7-amino-3cephem-4-carboxylic acidHCID 204323494-Allyl-2-fluoro-1-triphenylmethylimidazole

Product 1

HCID 704716253-Acetoxymethyl-7-(3-allylimidazol-2-yl)aminoceph-3-em-4-carboxylic acidYield 11.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-allyl-2-fluoro-1-triphenylmethyl imidazole (1.21 g.) and toluene-p-sulphonic acid monohydrate (0.635 g.) in DMF (8.5 ml.) was stirred at ambient temperature for 1 minute then at 80°. 3-Acetoxymethyl-7-aminoceph-3-em-4-carboxylic acid (0.904 g.) was added and the mixture was heated at 80° for 2.5 hours. The solution was evaporated to dryness in vacuo and water and EtOAc added to the residue. The aqueous layer was separated, evaporated to dryness, the residue redissolved in water and purified by preparative HPLC on Whatman "Partisil 10" using water/MeOH/HOAc 70:30:1 v/v/v as eluant to give 3-acetoxymethyl-7-(3-allylimidazol-2-yl)aminoceph-3-em-4-carboxylic acid (0.142 g.) having the following n.m.r. in d6DMSO+CD3COOD: 2.0 (s, 3H); 3.15 (d, 2H); 3.23 (d, 1H); 3.54 (d, 1H); 4.7 (d, 1H); 4.97 (d, 1H); 4.9- 5.2 (m, 3H); 5.48 (d, 1H); 5.8 (m, 1H); 6.3 (s, 1H).

Workup

  1. customat 80°
  2. temperaturethe mixture was heated at 80° for 2.5 hours
  3. customThe solution was evaporated to dryness in vacuo and water and EtOAc
  4. additionadded to the residue
  5. customThe aqueous layer was separated
  6. customevaporated to dryness
  7. dissolutionthe residue redissolved in water
  8. custompurified by preparative HPLC on Whatman "Partisil 10"

Sources & evidence

ORD record
ord-5df6fb41afaa447ea9720f76007044cb
Source dataset
uspto-grants-1985_01
Patent number
US04492692

Reaction notes

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