Thionyl Chloride → 6-bromo-4,7-difluoro-2,3-dihydro-1H-inden-1-one
Reaction equation
[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([CH2:9][CH2:10][C:11]([OH:13])=O)=[C:4]([F:14])[CH:3]=1.O=S(Cl)Cl.[Al+3].[Cl-].[Cl-].[Cl-]>C(Cl)Cl>[Br:1][C:2]1[C:7]([F:8])=[C:6]2[C:5]([CH2:9][CH2:10][C:11]2=[O:13])=[C:4]([F:14])[CH:3]=1Participants
5
Procedure
To a solution of 3-(4-bromo-2,5-difluorophenyl)propanoic acid (1.10 g) in DCM (20 mL) was added SOCl2 (2.45 g). The mixture was stirred at room temperature for 18 hours. The solvent was removed by evaporation under reduced pressure. The residue was dried under high vacuum to give a crude solid. To the residue was added AlCl3 (2.76 g) and the mixture heated to 130° C. The mixture was stirred at 130° C. for 2 hours and then cooled to room temperature. The resulting mixture was treated with ice water and then extracted with ethyl acetate (50 mL×3). The organic phase was washed with brine, dried over Na2SO4, and concentrated. The residue was purified by silica gel column chromatography eluting with petroleum ether/ethyl acetate (5:1) to give the subtitle compound as a light yellow solid. MS ESI+: m/z=247 [M+H]+.