Hydrochloric Acid → 5,7-Dichlorospiro[isoindoline-1,4'-piperidin]-3-one

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%).

1. temperatureThe mixture was heated
2. temperatureto reflux for 12 h
3. temperatureto cool to ambient and
4. customthen evaporated
5. customThe residue was used directly in the next step without further purification
6. dissolutionIt was dissolved in 150 mL of toluene
7. temperatureThe mixture was heated
8. temperatureto reflux overnight
9. customthe layers were separated
10. washThe organic layer was washed with brine
11. customdried
12. concentrationconcentrated
13. customto give the crude product
14. customIt was purified by column chromatography (PE:EtOAc=15:1)

ORDレコード

ord-ca81a611696f40a4b2d2b11cc0f754a0

出典データセット

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08383629B2