Reaktion #7100

Reaktionsgleichung

bromine

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

potassium acetate

→

title compound

Ausbeute 43.0%

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

Ausbeute 43.0%

Lösungsmittel

acetic acid

acetic acid

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

Quelle