反应详情

A stirred mixture of 22.6 g (0.120 mole) of 8-amino-6-methoxy-4-methylquinoline and 29.6 g (0.118 mole) of 6-bromo-N-(2-methyl-1-propyl)-hexanamide was heated in an oil bath (130° ) while 12.2 g (16.8 ml; 0.120 mole) of triethylamine was added dropwise over 30 minutes. The temperature of the bath was kept at 130° for 30 minutes, at 150° for 60 minutes, between 150° and 190° for 30 minutes, and at 190° for 30 minutes. The mixture was cooled to room temperature then diluted with 25 ml of ethyl acetate. The solid that separated was collected on a filter, extracted with boiling ethyl acetate (3×100 ml), then discarded. The filtrate and extracts were combined, then concentrated in vacuo to a solid; yield 44 g. The solid was dissolved in 130 ml of dichloromethane and purified by elution chromatography on a column (8 cm dia× 40 cm) of silica gel (1000 g; activity III) using 1 l of dichloromethane-ether (1:1), followed by 2 l of ether, as eluents. The fractions (100 ml each) containing pure product were combined then concentrated in vacuo. The fractions containing mixtures were concentrated in vacuo then triturated with diethyl ether to yield 25.4 g (60.2%) of crude product. The product was suitable for further transformation. Analytically pure compound was readily obtained (84% recovery) by recrystallization from methylene chloride and ether; mp 111°-112°.

1. additionwas added dropwise over 30 minutes
2. waitat 190° for 30 minutes
3. customThe solid that separated
4. customwas collected on a filter
5. extractionextracted with boiling ethyl acetate (3×100 ml)
6. concentrationconcentrated in vacuo to a solid
7. dissolutionThe solid was dissolved in 130 ml of dichloromethane
8. custompurified by elution chromatography on a column (8 cm dia× 40 cm) of silica gel (1000 g; activity III)
9. additionThe fractions (100 ml each) containing pure product
10. concentrationwere combined then concentrated in vacuo
11. additionThe fractions containing mixtures
12. concentrationwere concentrated in vacuo
13. customthen triturated with diethyl ether