Toluene → 4-[2-(2-Hydroxy-ethoxy)ethyl-piperazin-1-yl}-(2-iodophenyl)-methanone

2-iodobenzoic acid (20 g, 0.081 mol), toluene (20 ml) and thionyl chloride (30 ml, 0.41 mol) were charged into a reaction flask. The mixture was stirred and refluxed for 11 h. Toluene (40 ml) was added and the solvent and excess of thionylchloride were distilled off under reduced pressure. The process was repeated with 20 ml of toluene. The residue of 2-iodobenzoyl chloride was dissolved into THF (20 ml). 1-[2-(hydroxyethoxy)-ethyl]-piperazine (14.1 g, 0.081 mol), THF (100 ml), water (50 ml) and triethylamine (12.3 ml) were added into a reaction flask and stirred at icewater bath temperature. The previously prepared 2-iodobenzoyl chloride THF solution was slowly added to the reaction mixture. The temperature was kept below 20° C. during the addition. The reaction mixture was allowed to warm to room temperature and stirred 2 h at ambient temperature. 50 ml of water was added and THF was removed by distillation. The pH of the solution was checked and adjusted to 9-10. The water was extracted three times with dichloromethane (50 ml). The combined organic phase was evaporated yielding {4-[2-(2-hydroxy-ethoxy)ethyl-piperazin-1-yl}-(2-iodophenyl)-methanone as a yellowish oil, which was used without further purification. Yield 31 g.

1. temperaturerefluxed for 11 h
2. distillationthe solvent and excess of thionylchloride were distilled off under reduced pressure
3. dissolutionThe residue of 2-iodobenzoyl chloride was dissolved into THF (20 ml)
4. stirringstirred at icewater bath temperature
5. additionThe temperature was kept below 20° C. during the addition
6. stirringstirred 2 h at ambient temperature
7. customTHF was removed by distillation
8. extractionThe water was extracted three times with dichloromethane (50 ml)
9. customThe combined organic phase was evaporated

ORDレコード

ord-d10ecaf510324ca9b05cc64ee8fd0311

出典データセット

uspto-grants-2011_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07863441B2