Reacción #607495

Ecuación de reacción

sodium chloride

aluminum trichloride

144c

1-(4-bromo-2-fluorophenyl)-3-chloropropan-1-one

→

5-bromo-7-fluoro-2,3-dihydro-1H-inden-1-one

Rendimiento 30.4%

Disolventes

HCl

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe quenched reaction
2. 2
   workup.STIRRINGwas stirred for 40 min
3. 3
   Extracciónextracted with DCM (4000 mL×3)
4. 4
   LavadoThe combined organic phase was washed with saturated NaHCO3 solution (1000 mL), brine (2000 mL×2)
5. 5
   Secadodried with anhydrous sodium sulfate
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated under reduced pressure
8. 8
   OtroThe residue was purified by silica gel chromatography (PE/EA=50/1, 10/1)

Procedimiento

A mixture of sodium chloride (333 g, 5.69 mol) and aluminum trichloride (1270 g, 9.52 mol) was added to 144c (210 g, 0.79 mol) in several portions at 130° C. See FIG. 3. The neat reaction mixture was then stirred at 180° C. After 5 h the reaction mixture was poured into a stirred solution of ice water (1000 mL) and concentrated HCl (100 mL). The quenched reaction was stirred for 40 min and then extracted with DCM (4000 mL×3). The combined organic phase was washed with saturated NaHCO3 solution (1000 mL), brine (2000 mL×2), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (PE/EA=50/1, 10/1) to afford 55.0 g (30.4%) of 5-bromo-7-fluoro-2,3-dihydro-1H-inden-1-one 144d. 1H NMR (400 MHz, CDCl3) δ 7.37 (s, 1H), 7.10-7.12 (d, J=8.4 Hz, 1H), 3.04-3.10 (m, 2H), 2.50-2.66 (m, 2H).

Fuente