반응 #8762

반응 방정식

3-[3-(2-bromo-ethoxy)-phenyl]-thieno[2,3-d]isoxazole

potassium carbonate

1,2,3,4-tetrahydroisoquinoline

→

title compound

수율 61.5%

2-[2-(3-thieno[2,3-d]isoxazol-3-yl-phenoxy)-ethyl]-1,2,3,4-tetrahydroisoquinoline

수율 61.5%

용매

acetonitrile

반응 조건

후처리

1. 1
   온도Cool the reaction mixture
2. 2
   여과filter through a Waters Sep-Pak 1 g silica cartridge (ethyl acetate)
3. 3
   농축Combine the appropriate fractions and concentrate
4. 4
   기타to give a residue
5. 5
   기타Purify the residue by column (10 g silica) chromatography
6. 6
   workup.ADDITIONa graded solvent mixture of 10% ethyl acetate in dichloromethane to 20% ethyl acetate in dichloromethane
7. 7
   workup.DISSOLUTIONDissolve the free base in ethanol
8. 8
   농축concentrate to a sticky residue
9. 9
   기타triturate (methanol:ethyl acetate)
10. 10
    기타collect the powder
11. 11
    기타Recrystallize the powder (methanol:ethyl acetate)

실험 절차

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.

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