Реакция #65442

Уравнение реакции

1-[bis(4-fluorophenyl)methyl]piperazine

EDCI

HOBt

6-hydroxy-1,4-benzodioxin -2-carboxylic acid

→

6-Hydroxy-2-{4-[bis-(4-fluorophenyl)methyl]piperazin-1-ylcarbonyl}-1,4-benzodioxin

Выход 85.0%

Растворители

N,N-dimethylformamide

Условия реакции

Обработка

1. 1
   workup.WAITfor 12 hours at room temperature
2. 2
   Концентрированиеconcentrate the reaction mixture under reduced pressure
3. 3
   ЭкстракцияExtract the resulting amide with diethyl ether
4. 4
   Концентрированиеafter concentration to dryness
5. 5
   Другоеpurify the crude product by chromatography on a silica column (eluant

Методика

Under a nitrogen atmosphere, add 5.5 mmol of 1-[bis(4-fluorophenyl)methyl]piperazine, 5.5 mmol of EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide) and 5.5 mmol of HOBt (hydroxybenzotriazole) in succession to a solution at 0° C. of 5 nmml of 6-hydroxy-1,4-benzodioxin -2-carboxylic acid in 25 cm3 of N,N-dimethylformamide. Stir for 2 hours at 0° C. and then for 12 hours at room temperature, and concentrate the reaction mixture under reduced pressure. Extract the resulting amide with diethyl ether and then, after concentration to dryness, purify the crude product by chromatography on a silica column (eluant:petroleum ether then an increasing gradient of ethyl acetate in petroleum ether). 6-Hydroxy-2-{4-[bis-(4-fluorophenyl)methyl]piperazin-1-ylcarbonyl}-1,4-benzodioxin is thereby obtained in a yield of 85%. The product obtained is precipitated from 10 ml of pentane and is then filtered and recrystallised from cyclohexane.

Источник