Réaction #2383784

Équation de réaction

Phenylalanyl-β-alanine ethyl ester

ethyl bromoacetate

triethylamine

→

N-(carboethoxymethyl)phenylalanyl-β-alanine ethyl ester

Rendement 80.4%

Solvants

toluene

toluene

Conditions de réaction

Traitement

1. 1
   workup.ADDITIONwas added dropwise over 0.5 hours
2. 2
   AutreAfter completion of reaction
3. 3
   Autrethe resultant reaction mixture
4. 4
   Extractionwas subjected to extraction with ethyl acetate (20 g)
5. 5
   LavageThe organic layer was washed with a 2.5% aqueous solution of citric acid
6. 6
   AutreSubsequently, the solvent was removed

Mode opératoire

Phenylalanyl-β-alanine ethyl ester (10 g, 0.038 mol) and triethylamine (10.3 g, 0.1 mol) were suspended in toluene (45 g), and the suspension was heated to 60° C. To the resultant suspension, ethyl bromoacetate (9.3 g, 0.057 mol) suspended in toluene (5 g) was added dropwise over 0.5 hours, and then the resultant mixture was stirred for three hours. After completion of reaction, the resultant reaction mixture was subjected to extraction with ethyl acetate (20 g). The organic layer was washed with a 2.5% aqueous solution of citric acid. Subsequently, the solvent was removed, to thereby obtain N-(carboethoxymethyl)phenylalanyl-β-alanine ethyl ester (10.7 g, yield: 80.3%). The compound was dissolved in methanol, and a 48% aqueous solution of sodium hydroxide (6.6 g, 0.08 mol) was added to the methanol solution, and the resultant mixture was stirred for three hours. After completion of reaction, the solvent was removed, and the resultant residue was dissolved in water (20 mL), and then washed with ethyl acetate (10 g). Subsequently, hydrochloric acid was added to the aqueous layer, so as to attain a pH of 3.5. After being cooled, the resultant solution was subjected to filtration, to thereby obtain crude crystals. The crystals were recrystallized from a 20% aqueous solution of isopropyl alcohol, to thereby obtain compound 1 (6.0 g, yield: 67%).

Source