Reaktion #438315

Reaktionsgleichung

bis-(2-chloroethyl)amine

Tyramine

triethylamine

ethyl chloroformate

methyl chlorothioformate

bis-(2-Chloroethyl)amine hydrochloride

→

28

bis-(2-Chloroethyl)amino-4-hydroxyphenylaminomethanone

Lösungsmittel

ethyl acetate

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe mixture was heated
2. 2
   Temperaturunder reflux for 4 hours
3. 3
   Temperaturto cool
4. 4
   Sonstigepurified
5. 5
   Trocknenby dry flash column chromatography (silica gel, dichloromethane 200 cm3)
6. 6
   Einengenconcentrated in vacuo

Vorschrift

One pot method. bis-(2-Chloroethyl)amine hydrochloride 26 (200 mg, 1.1 mmol) was dissolved in dichloromethane (15 mL) and triethylamine (0.45 mL, 3.3 mmol) was added. The mixture was stirred for 5 minutes at ambient temperature and ethyl chloroformate or methyl chlorothioformate (1.32 mmol) was added. The mixture was stirred until no bis-(2-chloroethyl)amine remained by TLC (ethyl acetate). Tyramine (300 mg, 2.2 mmol) was added and the mixture was heated under reflux for 4 hours. the mixture was allowed to cool, purified by dry flash column chromatography (silica gel, dichloromethane 200 cm3) and concentrated in vacuo to yield prodrug 28 as an orange/brown oil (234 mg, 67% for methyl chlorothioformate and 229 mg, 64% for ethyl chloroformate).

Quelle