反应详情

A mixture of the product from the previous reaction (0.45 g), potassium carbonate (0.32g) and 1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine (0.51 g) in dimethylformamide (4.5 ml) and toluene (10 ml) was heated at reflux temperature for 6 hours, then left to stand at room temperature for 72 hours and then heated at reflux temperature for a further 4 hours. The cooled mixture was poured into water (300 ml) and extracted with ethyl acetate (3×40 ml). The combined organic extracts were extracted with dilute aqueous hydrochloric acid (5M; 3×30 ml) and the combined aqueous extracts basified by the addition of sodium hydroxide solution (5M). The aqueous phase was extracted with ethyl acetate (3×300 ml), dried over magnesium sulphate and the solvent removed under reduced pressure to yield a yellow oil. Purification by flash column chromatography on silica eluting with a 95:5 mixture of ethyl acetate and methanol afforded (S)-N-(7,8-methylenedioxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methylamine (0.3 g) as a clear oil. Citric acid (0.14 g) in ethanol (20 ml) was added to a solution of the oil in ethanol (20 ml) and the solvent was removed under reduced pressure to afford (S)-N-(7,8-methylenedioxy-2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-1-[1-(2-methoxyphenyl)piperid-4-yl]methyl-amine monocitrate (0.3 g) as a fawn solid; m.p 120-22° C., [α]D −35.9° (c=0.575, MeOH).

1. additionA mixture of the product
2. temperaturewas heated
3. temperatureat reflux temperature for 6 hours
4. waitleft
5. temperatureheated
6. temperatureat reflux temperature for a further 4 hours
7. extractionextracted with ethyl acetate (3×40 ml)
8. extractionThe combined organic extracts were extracted with dilute aqueous hydrochloric acid (5M; 3×30 ml)
9. additionthe combined aqueous extracts basified by the addition of sodium hydroxide solution (5M)
10. extractionThe aqueous phase was extracted with ethyl acetate (3×300 ml)
11. dry with materialdried over magnesium sulphate
12. customthe solvent removed under reduced pressure
13. customto yield a yellow oil
14. customPurification by flash column chromatography on silica eluting
15. additionwith a 95:5 mixture of ethyl acetate and methanol