Water → 4-(4-Fluoro-2-methoxyphenyl)-1-(7-fluoro-2-methylquinazolin-5-ylimino)-4-methyl-2-(trifluoromethyl)-pentan-2-ol

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Reaction Conditions

Reaction Steps

0.25 ml of titanium tetraethylate is added to 150 mg (0.48 mmol) of 4-(4-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)-pentanal and 85 mg (0.48 mmol) of 5-amino-7-fluoro-2-methylquinazoline in 8 ml of toluene, and the mixture is heated to 100° C. over 2 hours. After cooling, it is poured into water, and vigorous stirring is continued. The suspension is filtered through Celite, and it is rewashed thoroughly with ethyl acetate. The phases of the filtrate are separated, and it is extracted again with ethyl acetate. It is dried on sodium sulfate, and the solvent is removed in a vacuum. 220 mg of 4-(4-fluoro-2-methoxyphenyl)-1-(7-fluoro-2-methylquinazolin-5-ylimino)-4-methyl-2-(trifluoromethyl)-pentan-2-ol that is thus obtained in crude form is taken up in 8 ml of dichloromethane, and it is cooled to −70° C. 3 ml (3 mmol) of a 1 M titanium tetrachloride solution in dichloromethane is added in drops over 10 minutes, and it is allowed to heat for 4 hours to room temperature. The solution is poured into a saturated sodium bicarbonate solution and vigorously stirred for 5 minutes. It is extracted with ethyl acetate, washed with saturated sodium chloride solution and dried on sodium sulfate. After concentration by evaporation and chromatography on silica gel (dichloromethane/methanol 10%), 25 mg of the desired product is obtained.

Provenance & Evidence