7-fluoro-1,3-dihydroindol-2-one

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In an analogous manner 4- and 6-fluoro- and bromooxindoles are prepared, as well as 7-fluorooxindole, 7-bromooxindole, 7-methyloxindole, 4,6-difluorooxindole, 4,7-dichlorooxindole, 5,7-difluorooxindole, 5-n-butyl-7-fluorooxindole, 7-cyclohexyloxindole and 7-cyclopropyloxindole.

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Fluoro-3-(methylsulfanyl)-1,3-dihydro-2H-indol-2-one (270.5 g) was dissolved in water (2000 g) and admixed with sodium bisulfite (300 g). The mixture was heated to reflux, in the course of which it was vigorously stirred. After 2.25 h, the mixture was cooled to 25° C. and isolated by filtration on a suction filter. It was washed twice with water (500 g each time) and then dried under reduced pressure (<50 mbar, 50° C.). This gave 7-fluoro-1,3-dihydro-2H-indol-2-one as a white solid (206.3 g, 95.1% by weight, 95% yield). The mixture was heated to reflux, in the course of which it isolated by filtration on a suction filter It was washed twice with water (500 g each time) dried under reduced pressure (<50 mbar, 50° C.)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Fluoro-3-(methylsulfanyl)-1,3-dihydro-2H-indol-2-one (270.5 g) was dissolved in water (2000 g) and admixed with sodium bisulfite (300 g). The mixture was heated to reflux, in the course of which it was vigorously stirred. After 2.25 h, the mixture was cooled to 25° C. and isolated by filtration on a suction filter. It was washed twice with water (500 g each time) and then dried under reduced pressure (<50 mbar, 50° C.). This gave 7-fluoro-1,3-dihydro-2H-indol-2-one as a white solid (206.3 g, 95.1% by weight, 95% yield). The mixture was heated to reflux, in the course of which it isolated by filtration on a suction filter It was washed twice with water (500 g each time) dried under reduced pressure (<50 mbar, 50° C.)

Conditions: temp:-45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-fluoro-1,3-dihydro-2H-indol-2-one (8.0 g, 52.9 mmol) was slurried in H2SO4 (conc., 86 ml) and the mixture cooled to −45° C. A solution of fuming nitric acid (>90%, 3.34 g, 52.9 mmol) in H2SO4 (20 ml) was added drop wise, while maintaining the temperature at −45° C. throughout the addition. The mixture was allowed to slowly warm to RT and stirred overnight. The mixture was poured into stirred ice-cold water (1500 ml). A white precipitate resulted, and the slurry was aged at 0° C. for 1 hour. The solid was collected by filtration, triturated with cold water (2×), and dissolved into EtOAc (1 L). This solution was washed with basic brine (containing sodium bicarbonate), dried over Na2SO4, filtered, and the volatiles removed in vacuum to give the titled compound. while maintaining the temperature at −45° C. throughout the addition to slowly warm to RT The mixture was poured A white precipitate resulted the slurry was aged at 0° C. for 1 hour The solid was collected by filtration triturated with cold water (2×) dissolved into EtOAc (1 L) This solution was washed with basic brine (containing sodium bicarbonate) dried over Na2SO4 filtered the volatiles removed in vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7-Fluoroindolin-2-one (800 mg, 5293 μmol) was taken up in 30 mL of boiling water. Br2 (273 μL, 5293 μmol) and KBr (1260 mg, 10586 μmol) were added dropwise in 5 mL of water over 10 minutes. A white precipitate began to form as the solution was added. The mixture was stirred for 20 minutes. The mixture was then chilled in an ice bath for 30 minutes, washed with 30 mL of a saturated NaHCO3 solution and extracted twice with 50 mL of EtOAc. The organic layers were concentrated and purified with silica gel column chromatography, eluting with 0-35% EtOAc/hexane to give 5-bromo-7-fluoroindolin-2-one (913 mg, 75% yield). MS m/z: 230 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 3.58 (s, 2H), 7.20 (dd, J=10.07, 0.88 Hz, 2H), 7.63 (s, 1H). to form as the solution was added The mixture was then chilled in an ice bath for 30 minutes washed with 30 mL of a saturated NaHCO3 solution extracted twice with 50 mL of EtOAc The organic layers were concentrated purified with silica gel column chromatography eluting with 0-35% EtOAc/hexane

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a 250 mL round bottom flask was added ethyl 2-(3-fluoro-2-nitrophenyl)acetate (3.1 g, 14 mmol), iron (3.8 g, 68 mmol), and 50 mL of AcOH. The reaction mixture was heated at 60° C. for 1 hour. The reaction mixture was concentrated and dissolved in 100 mL of EtOAc, filtered, and washed with 50 mL of a saturated NaHCO3 solution. The organic layer was concentrated and purified with silica gel column chromatography, eluting with 40% EtOAc/hexane to give 7-fluoroindolin-2-one (1.2 g, 58% yield) as a white solid. MS m/z: 152 (M+1). 1H NMR (400 MHz, CDCl3) δ ppm 3.58 (s, 2H), 6.94-7.04 (m, 3H). The reaction mixture was concentrated dissolved in 100 mL of EtOAc filtered washed with 50 mL of a saturated NaHCO3 solution The organic layer was concentrated purified with silica gel column chromatography eluting with 40% EtOAc/hexane