4-chloro-2-fluoro-1-methylbenzene

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

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

Procedure: 361.5 g of 4-chloro-2-fluorotoluene, 520 g of chlorobenzene, 6 g of conc. H2SO4, 467 g of 47% strength hydrobromic acid and 2.7 g of 2,2'-azobis(2-methylpropionitrile) were mixed at 70° C. in a 4 l stirred apparatus. 620.5 g of a 10% strength aqueous hydrogen peroxide solution and a solution of 16.5 g of 2,2'-azobis(2-methylpropionitrile) in 270 g of chlorobenzene were simultaneously added dropwise over the course of 1.5 hours. The mixture was then stirred at 70° C. for 1 hour. GC analysis of the org. phase: The mixture was then stirred at 70° C. for 1 hour

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

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

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 45 ml pyridine in 800 ml tetrahydrofuran (THF) was added dropwise 50 ml trimethylacetyl chloride. The mixture was stirred 3 hrs. at room temperature, 4.0 g cuprous iodide was added, and the mixture stirred for 1 hr. longer. The mixture was then cooled to -40° C. and a Grignard reagent prepared from 45 ml 2-fluoro-4-chlorotoluene and 10 g magnesium in 300 ml THF was added dropwise The reaction mixture was stirred overnight at room temperature, ammonium chloride solution added, and the product was extracted and isolated to give 90 g of an oil used directly in the next reaction. the mixture stirred for 1 hr was added dropwise The reaction mixture was stirred overnight at room temperature the product was extracted isolated

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

Procedure: A mixture of 2-fluoro-4-chlorotoluene (25.05 g), KMnO4 (55.04 g) and water (400 ml) is heated to reflux for about 5 hr. The reaction is then worked up by filtering while hot through Celite and the filtrate is acidified with 2 N HCl. White crystals are filtered off, dissolved in ether and washed with water and brine, dried over sodium sulfate, filtered and evaporated to yield 2-fluoro-4-chlorobenzoic acid. is heated to reflux for about 5 hr by filtering while hot through Celite White crystals are filtered off dissolved in ether washed with water and brine dried over sodium sulfate filtered evaporated

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

Procedure: A mixture of 2-fluoro-4-chlorotoluene (25.05 g), KMnO4 (55.04 g) and water (400 ml) is heated to reflux for about 5 hr. The reaction is then worked up by filtering while hot through Celite and the filtrate is acidified with 2 N HCl. White crystals are filtered off, dissolved in ether and washed with water and brine, dried over sodium sulfate, filtered and evaporated to yield 2-fluoro-4-chlorobenzoic acid. is heated to reflux for about 5 hr by filtering while hot through Celite White crystals are filtered off dissolved in ether washed with water and brine dried over sodium sulfate filtered evaporated

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

Procedure: 361.5 g of 4-chloro-2-fluorotoluene, 520 g of chlorobenzene, 6 g of conc. H2SO4, 467 g of 47% strength hydrobromic acid and 2.7 g of 2,2'-azobis(2-methylpropionitrile) were mixed at 70° C. in a 4 l stirred apparatus. 620.5 g of a 10% strength aqueous hydrogen peroxide solution and a solution of 16.5 g of 2,2'-azobis(2-methylpropionitrile) in 270 g of chlorobenzene were simultaneously added dropwise over the course of 1.5 hours. The mixture was then stirred at 70° C. for 1 hour. GC analysis of the org. phase: The mixture was then stirred at 70° C. for 1 hour

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere, to a solution (75 mL) of N,N,N′,N′-tetramethylethylenediamine (16.15 g) in dry tetrahydrofuran was added a solution (139 mL) of 1 mol/L-sec-butyllithium in hexane/cyclohexane under cooling (dry ice-acetone bath) at not higher than −60° C., and the mixture was stirred at the same temperature for 20 min. The mixture was further cooled to −78° C., and a solution (50 mL) of 4-chloro-2-fluoro-1-methylbenzene (18.26 g) in dry tetrahydrofuran was added thereto. After the reaction mixture was stirred at the same temperature for 30 min, a solution (275 mL) of hexachloroethane (119.6 g) in dry tetrahydrofuran was added dropwise thereto. The mixture was stirred at the same temperature for 30 min to gradually warm to room temperature. To the reaction mixture was added 6 mol/L hydrochloric acid to adjust to pH=5 and the mixture was concentrated. The residue was partitioned between ether and water, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was placed on a glass filter, washed with a small amount of ether and filtrated. The filtrate was concentrated and evaporated under reduced pressure. The fraction at the boiling point of 48° C. (1.5 Torr) was collected to give the title compound as a colorless oil (yield: 19 g). After the reaction mixture was stirred at the same temperature for 30 min The mixture was stirred at the same temperature for 30 min to gradually warm to room temperature the mixture was concentrated The residue was partitioned between ether and water the organic layer was washed with saturated brine dried over anhydrous magnesium sulfate concentrated filter washed with a small amount of ether filtrated The filtrate was concentrated evaporated under reduced pressure The fraction at the boiling point of 48° C. (1.5 Torr) was collected

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 45 ml pyridine in 800 ml tetrahydrofuran (THF) was added dropwise 50 ml trimethylacetyl chloride. The mixture was stirred 3 hrs. at room temperature, 4.0 g cuprous iodide was added, and the mixture stirred for 1 hr. longer. The mixture was then cooled to -40° C. and a Grignard reagent prepared from 45 ml 2-fluoro-4-chlorotoluene and 10 g magnesium in 300 ml THF was added dropwise The reaction mixture was stirred overnight at room temperature, ammonium chloride solution added, and the product was extracted and isolated to give 90 g of an oil used directly in the next reaction. the mixture stirred for 1 hr was added dropwise The reaction mixture was stirred overnight at room temperature the product was extracted isolated

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

Procedure: A mixture of 2-fluoro-4-chlorotoluene (25.05 g), KMnO4 (55.04 g) and water (400 ml) is heated to reflux for about 5 hr. The reaction is then worked up by filtering while hot through Celite and the filtrate is acidified with 2 N HCl. White crystals are filtered off, dissolved in ether and washed with water and brine, dried over sodium sulfate, filtered and evaporated to yield 2-fluoro-4-chlorobenzoic acid. is heated to reflux for about 5 hr by filtering while hot through Celite White crystals are filtered off dissolved in ether washed with water and brine dried over sodium sulfate filtered evaporated

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

Procedure: 361.5 g of 4-chloro-2-fluorotoluene, 520 g of chlorobenzene, 6 g of conc. H2SO4, 467 g of 47% strength hydrobromic acid and 2.7 g of 2,2'-azobis(2-methylpropionitrile) were mixed at 70° C. in a 4 l stirred apparatus. 620.5 g of a 10% strength aqueous hydrogen peroxide solution and a solution of 16.5 g of 2,2'-azobis(2-methylpropionitrile) in 270 g of chlorobenzene were simultaneously added dropwise over the course of 1.5 hours. The mixture was then stirred at 70° C. for 1 hour. GC analysis of the org. phase: The mixture was then stirred at 70° C. for 1 hour