반응 #477322

반응 방정식

4-oxo-piperidine-1-carboxylic acid tert-butyl ester

4-methoxy-benzylamine

3,5-dichloro-2-iodobenzoyl chloride

Et3N

HCl

→

desired product

수율 118.5%

5,7-dichlorospiro[isoindoline-1,4′-piperidin]-3-one

수율 118.5%

용매

toluene

반응 조건

후처리

1. 1
   온도The mixture was heated
2. 2
   온도to reflux for 12 h
3. 3
   온도to cool to ambient and
4. 4
   기타then evaporated
5. 5
   기타The residue was used directly in the next step without further purification
6. 6
   workup.DISSOLUTIONIt was dissolved in 150 mL of toluene
7. 7
   온도The mixture was heated
8. 8
   온도to reflux overnight
9. 9
   기타the layers were separated
10. 10
    세척The organic layer was washed with brine
11. 11
    기타dried
12. 12
    농축concentrated
13. 13
    기타to give the crude product
14. 14
    기타It was purified by column chromatography (PE:EtOAc=15:1)

실험 절차

A 500-mL flask was charged with 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (7.0 g, 35 mmol), 4-methoxy-benzylamine (4.8 g, 35 mmol) and 120 mL of toluene. The mixture was heated to reflux for 12 h. The yellow-orange solution was allowed to cool to ambient and then evaporated. The residue was used directly in the next step without further purification. It was dissolved in 150 mL of toluene. Then 3,5-dichloro-2-iodobenzoyl chloride (9.4 g, 28 mmol) and Et3N (4.5 g, 44 mmol) was added. The mixture was heated to reflux overnight. The mixture was acidified with 0.5 N aq HCl, and the layers were separated. The organic layer was washed with brine, dried and concentrated to give the crude product. It was purified by column chromatography (PE:EtOAc=15:1) to give the desired product (9.0 g, 42%).

출처