反应详情

To a stirred 0° C. solution of 1-[1-(2,2,2-trifluoro-ethyl)-piperidin-4-yl]-indole (180 mg, 0.64 mmol) in dry ether (3 mL ) was added oxalyl chloride (0.06 mL, 0.7 mmol). The reaction mixture was warmed to ambient temperature for 30 minutes. An additional amount of oxalyl chloride (0.04 mL, 0.5 mmol ) was added. After 30 minutes, a yellow precipitate formed which was filtered with the exclusion of moisture and air, and washed with a small amount of ether. The collected precipitant was dissolved in dry methylene chloride (10 mL) and treated with isopropyl(1-methyl) indol-3-yl)acetimidate hydrochloride (190 mg, 0.71 mmol ) followed by slow addition of triethylamine (0.44 mL, 3.2 mmol) at 0° C. After 4 hours at ambient temperature, p-toluene sulfonic acid monohydrate (0.61 g, 3.2 mmol) was added. After 30 minutes the mixture was quenched with saturated aqueous sodium hydrogen carbonate solution (40 mL). The organic phase was separated, washed with water, dried, and evaporated. The residue was recrystallized from hot dioxane and yielded 100 mg of bright orange crystals. Recrystallization of the mother liquor from THF yielded a second crop (60 mg). Yield: 160 mg of bright orange crystals (49% of theory) M.Pt.: >250° C.

1. customa yellow precipitate formed which
2. filtrationwas filtered with the exclusion of moisture and air
3. washwashed with a small amount of ether
4. dissolutionThe collected precipitant was dissolved in dry methylene chloride (10 mL)
5. waitAfter 4 hours at ambient temperature
6. customAfter 30 minutes the mixture was quenched with saturated aqueous sodium hydrogen carbonate solution (40 mL)
7. customThe organic phase was separated
8. washwashed with water
9. customdried
10. customevaporated
11. customThe residue was recrystallized from hot dioxane