5-amino-8-fluoroquinolin-2(1H)-one → 5-{[(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-8-fluoroquinolin-2(1H)-one

Participants

Reaction Steps

In the same way as in Example 148, 300 mg (0.88 mmol) of (2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexanal, 156 mg (0.88 mmol) of 5-amino-8-fluoroquinolin-2(1H)-one and 0.55 ml of titanium tert-butoxide is reacted to give 5-{[(2R,4R)-4-(3-chloro-4-fluoro-2-methoxyphenyl)-2-hydroxy-2-(trifluoromethyl)hexylidene]amino}-8-fluoroquinolin-2(1H)-one. 480 mg of crude imine are cyclized in the same way as in Example 148 at −30° C. with 7.6 ml (7.6 mmol) of 1 M boron tribromide solution to give the desired product. Column chromatography on silica gel (hexane/ethyl acetate 0-70%) yields 119 mg of desired product.

Provenance & Evidence