反应详情

A mixture of 1-indanylacetic acid (CIX, EXAMPLE 66, 7.4 g, 42 mmol) and triethylamine (29.3 ml, 210 mmol), and 1-(4-methoxyphenyl)piperazine dihydrochloride (LXV, 13.3 g, 50.4 mmol) in methylene chloride (420 ml) is stirred at 20-25° under a nitrogen atmosphere. Diethylcyanophosphonate (12.7 ml, 84 mmol) is added over a period of 10 min at 20-25°. After the stirring for 3 hr, the reaction is quenched with sodium hydroxide (20%) and extracted with methylene chloride (2×500 ml). The organic phase is washed with saline, dried (magnesium sulfate), filtered and concentrated under reduced pressure. The crude product is purified by crystallization from ethyl acetate/methanol. The mother liquor is purified by liquid chromatography on silica gel 60 (230-400 mesh, 400 g), eluting with hexane/ethyl acetate (1/2). The appropriate fractions homogeneous by TLC are combined and concentrated under reduced pressure to give a solid. Both solids are combined to give the title compound, mp=111-112°; NMR (CDCl3, TMS) 7.26-6.83, 3.77 and 3.85-1.54 δ.

1. customthe reaction is quenched with sodium hydroxide (20%)
2. extractionextracted with methylene chloride (2×500 ml)
3. washThe organic phase is washed with saline
4. dry with materialdried (magnesium sulfate)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe crude product is purified by crystallization from ethyl acetate/methanol
8. customThe mother liquor is purified by liquid chromatography on silica gel 60 (230-400 mesh, 400 g)
9. washeluting with hexane/ethyl acetate (1/2)
10. concentrationconcentrated under reduced pressure
11. customto give a solid