Реакция #47962

Уравнение реакции

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

→

(±)-6-chloro-4-(4-fluorophenyl)-4-propyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one

Выход 100.4%

Растворители

ethyl acetate

Условия реакции

Обработка

1. 1
   ДругоеA balloon of hydrogen was bubbled into the stirring mixture
2. 2
   ДругоеThe reaction was purged with nitrogen
3. 3
   Фильтрацияfiltered through a pad of celite
4. 4
   Концентрированиеthe filtrate concentrated in vacuo

Методика

To a solution of 4-allyl-6-chloro-4-(4-fluorophenyl)-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (22.1 g, 55.4 mmol) in ethyl acetate (450 mL) and under a nitrogen atmosphere was added 10% palladium on carbon (224 mg). A balloon of hydrogen was bubbled into the stirring mixture. The reaction was then stirred over night under an atmosphere of hydrogen. The reaction was purged with nitrogen, filtered through a pad of celite and the filtrate concentrated in vacuo to give 22.3 gm (100%) of (±)-6-chloro-4-(4-fluorophenyl)-4-propyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one as a white solid. Further purification by chiral chromatography (ChiralPak AD packing, 30% iPrOH/heptane with DEA modifier at 1.0 mL/L) followed by crystallization from hexanes provided individual enantiomers of 6-chloro-4-(4-fluorophenyl)-4-propyl-3-(2,2,2-trifluoroethyl)-3,4-dihydroquinazolin-2(1H)-one (Peak 1 and Peak 2). Data for Peak 2: 1H NMR (d6-DMSO, 400 MHz) δ 10.02 (s, 1H); 7.43 (m, 2H); 7.20 (m, 3H); 6.84 (d, J=8.61 Hz, 1H); 6.59 (d, J=2.19 Hz, 1H); 3.80 (q, J=9.34 Hz, 2H); 2.33 (m, 2H); 1.24 (m, 1H); 0.94 (m, 1H); 0.89 (t, J=6.87 Hz, 3H). Exact Mass (Electrospray, M+H): Calc'd, 401.1039; Found, 401.1040. [α]D=−6.7° (c0.0045, MeOH). Optical rotation for Peak 1: [α]D=+5.2° (c0.0062, MeOH).

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