Citric Acid → 4-allyl-6-chloro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

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Reaction Steps

To a −40° C. solution of 6-chloro-4-(4-fluorophenyl)-4-hydroxy-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (21.2 g, 56.6 mmol) in anhydrous THF (170 mL) was added triethylamine (39.4 mL, 283 mmol). The reaction was stirred for 5 min and then thionyl chloride (4.4 mL, 59.4 mmol) was added drop wise maintaining the temperature <−20° C. After 25 min, 1.0M allylmagnesium bromide in THF (170 mL, 170 mmol) was added over 35 min maintaining the temperature <−10° C. The reaction was stirred <−5° C. over 30 min and then poured into a vigorously stirred mixture of aqueous 10% citric acid (150 mL), ice (50 g), and ethyl acetate (200 mL). The aqueous phase was extracted with ethyl acetate (3×100 mL). The combined organics were washed with water (100 mL), brine (100 mL), dried over Na2SO4, filtered, and concentrated in vacuo to give a crude brown oil. The oil was dissolved in methylene chloride (100 mL) and stirred 1 hr. The resulting precipitate was collected by vacuum filtration and dried under vacuum for 16 h to give racemic 4-allyl-6-chloro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one as an off-white solid.

Provenance & Evidence