Methanol → HCID 10475235, compound

A mixture of 4-(4-fluorobenzoyl)piperidine(5 mmol) and 2-(4-nitro-phenyl)oxirane (5 mmol) was refluxed in 30 ml of isopropanol for 4 h. This solution was then concentrated on a rotary evaporator and diluted with ethyl acetate. This mixture was then washed with brine, the resulting organic layer was dried and concentrated in vacuo. The crude product was dissolved in dichloromethane (50 ml) and was added with methanesulfonyl chloride (2 eq.) and triethylamine (3 eq.) at 0° C. The reaction mixture was stirred at room temperature for 1 h. This solution was then concentrated on a rotary evaporator and dissolved in THF (50 ml), added triethylamine (3 eq.), followed by the addition of excess methanol (>10 eq.). After 12 hours stirring at 80° C., this solution is concentrated on a rotary evaporator and diluted with ethyl acetate. The organic layer was extracted 3 times with dichloromethane, dried and concentrated in vacuo. The residue was purified by column chromatography (ethyl acetate:hexane=1:1). The resulting (4-fluoro-phenyl)-{1-[2-methoxy-2-(4-nitro-phenyl)-ethyl]-piperidin-4-yl}-methanone was dissolved in dichloromethane and the solution was treated with a solution of HCl in ethyl ether. The resulting precipitate was filtered to give (4-fluoro-phenyl)-{1-[2-methoxy-2-(4-nitro-phenyl)-ethyl]-piperidin-4-yl}-methanone; hydrochloride

1. concentrationThis solution was then concentrated on a rotary evaporator
2. additiondiluted with ethyl acetate
3. washThis mixture was then washed with brine
4. customthe resulting organic layer was dried
5. concentrationconcentrated in vacuo
6. dissolutionThe crude product was dissolved in dichloromethane (50 ml)
7. concentrationThis solution was then concentrated on a rotary evaporator
8. dissolutiondissolved in THF (50 ml)
9. stirringAfter 12 hours stirring at 80° C.
10. concentrationthis solution is concentrated on a rotary evaporator
11. additiondiluted with ethyl acetate
12. extractionThe organic layer was extracted 3 times with dichloromethane
13. customdried
14. concentrationconcentrated in vacuo
15. customThe residue was purified by column chromatography (ethyl acetate:hexane=1:1)
16. dissolutionThe resulting (4-fluoro-phenyl)-{1-[2-methoxy-2-(4-nitro-phenyl)-ethyl]-piperidin-4-yl}-methanone was dissolved in dichloromethane
17. additionthe solution was treated with a solution of HCl in ethyl ether
18. filtrationThe resulting precipitate was filtered

ORD record

ord-bfeb4e421698453a92eb745ca37a3c75

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06770659B2