Ethyl bromoacetate → HCID 11279546, compound

HRID 2296602Notes

Reaction equation

HRID 2296602 reaction equation
[CH2:1]([O:3][C:4](=[O:19])[CH2:5][CH2:6][NH:7][C:8](=[O:18])[C@H:9]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[NH2:10])[CH3:2].C(N(CC)CC)C.Br[CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30]>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4](=[O:19])[CH2:5][CH2:6][NH:7][C:8](=[O:18])[C@H:9]([CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)[NH:10][CH2:28][C:29]([O:31][CH2:32][CH3:33])=[O:30])[CH3:2]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 8471TriethylamineHCID 11207786HCID 11207786, compound

Product 1

HCID 11279546HCID 11279546, compoundYield 80.4%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
60 °C

Procedure

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%).

Workup

  1. additionwas added dropwise over 0.5 hours
  2. customAfter completion of reaction
  3. customthe resultant reaction mixture
  4. extractionwas subjected to extraction with ethyl acetate (20 g)
  5. washThe organic layer was washed with a 2.5% aqueous solution of citric acid
  6. customSubsequently, the solvent was removed

Sources & evidence

ORD record
ord-452bab8ea0d741f2bdf99889bccfa69d
Source dataset
uspto-grants-2002_12
Patent number
US06489291B1

Reaction notes

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