反应详情

温度

75 °C

Mix 3-[3-(2-bromo-ethoxy)-phenyl]-thieno[2,3-d]isoxazole (0.400 g, 1.23 mmol), potassium carbonate (0.345 g, 2.50 mmol), 1,2,3,4-tetrahydroisoquinoline (0.532 g, 3.99 mmol) and acetonitrile (5.0 mL) and heat at 75° C., overnight. Cool the reaction mixture and filter through a Waters Sep-Pak 1 g silica cartridge (ethyl acetate). Combine the appropriate fractions and concentrate to give a residue. Purify the residue by column (10 g silica) chromatography using a graded solvent mixture of 10% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane. Dissolve the free base in ethanol and acidify with ethereal hydrochloric acid, concentrate to a sticky residue, triturate (methanol:ethyl acetate) and collect the powder. Recrystallize the powder (methanol:ethyl acetate) to obtain the title compound as white crystals (0.285 g, 56%). mp=202–204° C. Microanalysis (C, H, N) is consistent with the final, desired compound.

1. temperatureCool the reaction mixture
2. filtrationfilter through a Waters Sep-Pak 1 g silica cartridge (ethyl acetate)
3. concentrationCombine the appropriate fractions and concentrate
4. customto give a residue
5. customPurify the residue by column (10 g silica) chromatography
6. additiona graded solvent mixture of 10% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane
7. dissolutionDissolve the free base in ethanol
8. concentrationconcentrate to a sticky residue
9. customtriturate (methanol:ethyl acetate)
10. customcollect the powder
11. customRecrystallize the powder (methanol:ethyl acetate)