Imidazole → HCID 21269041, compound

HRID 1195056Notes

Reaction equation

HRID 1195056 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:13]/[O:14][CH2:15][CH2:16]Br)/[C:8]([O:10]CC)=[O:9])[N:6]=1.[NH:18]1[CH:22]=[CH:21][N:20]=[CH:19]1>C(#N)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:13]/[O:14][CH2:15][CH2:16][N:18]2[CH:22]=[CH:21][N:20]=[CH:19]2)/[C:8]([OH:10])=[O:9])[N:6]=1

Participants

4

Reactant 2

HCID 795ImidazoleHCID 88629807HCID 88629807, compound

Product 1

HCID 21269041HCID 21269041, compoundYield 93.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

16.1 g of ethyl 2-(2-amino-4-thiazolyl)-2-[(Z)-(2-bromoethoxy)imino]-acetate and 17 g of imidazole are boiled under reflux for 4 hours in 160 ml of acetonitrile. The mixture is evaporated to dryness under reduced pressure, the residue is taken up in 150 ml of water, 25 ml of aqueous 3N sodium hydroxide solution and 100 ml of ethyl acetate and the aqueous phase is extracted twice with 100 ml of ethyl acetate each time. The organic phase are combined, washed with a small amount of water and evaporated. The residue is saponified at 50° C. for 1.5 hours with 100 ml of aqueous 1N sodium hydroxide solution and 100 ml of methanol. After the addition of 100 ml of 1N aqueous hydrochloric acid, the mixture is evaporated. The evaporation residue is crystallized using 250 ml of methanol and the crystallizate is suction filtered. There are obtained 13.2 g of crude 2-(2-amino-4-thiazolyl)-2-[(Z)-(2-imidazol-1-yl-ethoxy)imino]-acetic acid. For purification, a solution of 11 g of crude product in 100 ml of water is adsorbed on 200 ml of DOWEX 50 W (ion exchange resin; H+ form). The product is recovered by elution with 2.5% aqueous ammonia solution. After evaporation of the solvent, the product is crystallized using methanol. There are obtained 5.6 g of 2-(2-amino-4-thiazolyl)-2-[(Z)-(2-imidazol-1-yl-ethoxy)imino]-acetic acid of melting point 166° C. (decomposition).

Workup

  1. customThe mixture is evaporated to dryness under reduced pressure
  2. extraction25 ml of aqueous 3N sodium hydroxide solution and 100 ml of ethyl acetate and the aqueous phase is extracted twice with 100 ml of ethyl acetate each time
  3. washwashed with a small amount of water
  4. customevaporated
  5. additionAfter the addition of 100 ml of 1N aqueous hydrochloric acid
  6. customthe mixture is evaporated
  7. customThe evaporation residue is crystallized
  8. filtrationfiltered

Sources & evidence

ORD record
ord-65ce929ea56045cba2fe3f294d304678
Source dataset
uspto-grants-1989_03
Patent number
US04816582

Reaction notes

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