Реакция #7100

Уравнение реакции

bromine

3-(1′,2′-dihydro-2′-oxospiro[cyclohexane-1,3′-[3H]indol]-5′-yl)-5-fluorobenzonitrile

potassium acetate

→

title compound

Выход 43.0%

3-(7′-Bromo-1′,2′-dihydro-2′-oxospiro[cyclohexane-1,3′-[3H]indol]-5′-yl)-5-fluoro-benzonitrile

Выход 43.0%

Растворители

acetic acid

acetic acid

Условия реакции

Обработка

1. 1
   workup.ADDITIONwas poured onto ice (20 g)
2. 2
   ДругоеThe layers were separated
3. 3
   Экстракцияthe aqueous layer was extracted with dichloromethane (2×10 mL)
4. 4
   Промывкаwashed sequentially with 10% aqueous sodium thiosulfate (20 mL), water (2×10 mL), saturated sodium bicarbonate (10 mL) and brine (15 mL)
5. 5
   Сушкаdried over MgSO4
6. 6
   ФильтрацияThe solution was filtered
7. 7
   Концентрированиеconcentrated in vacuo
8. 8
   Другоеthe residue was purified by flash column chromatography on silica gel (eluting with 30% EtOAc/hexane)

Методика

A mixture of 3-(1′,2′-dihydro-2′-oxospiro[cyclohexane-1,3′-[3H]indol]-5′-yl)-5-fluorobenzonitrile (0.40 g, 1.23 mmol) and potassium acetate (0.13 g, 1.3 mmol) in glacial acetic acid (3 mL) at room temperature was treated with a solution of bromine (1.05 eq, 0.21 g, 1.3 mmol) in a glacial acetic acid (3 mL). After stirring for 1 h the mixture was poured onto ice (20 g). The layers were separated and the aqueous layer was extracted with dichloromethane (2×10 mL). The organic layers were combined, washed sequentially with 10% aqueous sodium thiosulfate (20 mL), water (2×10 mL), saturated sodium bicarbonate (10 mL) and brine (15 mL) and dried over MgSO4. The solution was filtered, concentrated in vacuo, and the residue was purified by flash column chromatography on silica gel (eluting with 30% EtOAc/hexane) to give the title compound (0.21 g, 43%) as an oil which crystallized upon addition of 10% EtOAc/hexanes, mp 217° C. 1H NMR (CDCl3; 300 MHz) δ 1.56–2.04 (m, 10H), 7.33 (dddd, 1H, J=1.25, 2.3, 3.6 and 9.0 Hz), 7.45 (m, 1H), 7.47 (m, 2H), 7.54 (m, 1H), 7.60 (m, 1H). MS ((−)−ESI) m/z 399 [M−]. Anal. Calcd for C20H16BrFN2O1: C, 60.17; H, 4.04; N, 7.02. Found: C, 60.03; H, 4.08; N, 6.83.

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