反应详情

A cold (-40°) slurry of 1.8 g (0.0135 mole) of anhydrous aluminum chloride in 60 ml of tetrahydrofuran was added to an equally cold suspension of 1.5 g (0.039 mole) of lithium aluminum hydride in 30 ml of tetrahydrofuran. The mixture was stirred and allowed to warm to -10°. To it was added dropwise a solution of 4.4 g (0.0103 mole) of 4-(3-hydroxypropyl)-N-(6-methoxy-4-methyl-8-quinolinyl)-1-piperazinehexanamide in 15 ml of tetrahydrofuran. The mixture was stirred for 2 hr, then treated with 7 ml of 30% sodium hydroxide solution and enough water to clarify the supernatant and finally filtered through supercell. The filtrate was concentrated in vacuo to remove tetrahydrofuran, diluted with dichloromethane, washed with water, dried, and concentrated to dryness. The residue was chromatographed over 200 g of silica gel with a 15:84:1 mixture of methanol:ethyl acetate-triethylamine. That portion of the eluant containing the product, Rf(silica--25:74:1 mixture of methanol:ethyl acetate:triethylamine)=0.33, was concentrated to dryness in vacuo. Recrystallization of the residue from 2-propanol afforded 2.1 g (49%) of the title compound, mp 100°-102°.

1. temperatureto warm to -10°
2. stirringThe mixture was stirred for 2 hr
3. filtrationfinally filtered through supercell
4. concentrationThe filtrate was concentrated in vacuo
5. customto remove tetrahydrofuran
6. additiondiluted with dichloromethane
7. washwashed with water
8. customdried
9. concentrationconcentrated to dryness
10. customThe residue was chromatographed over 200 g of silica gel with a 15:84:1 mixture of methanol
11. additionThat portion of the eluant containing
12. additionthe product, Rf(silica--25:74:1 mixture of methanol:ethyl acetate:triethylamine)=0.33
13. concentrationwas concentrated to dryness in vacuo
14. customRecrystallization of the residue from 2-propanol