2-chloro-4-fluoroaniline

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:

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [1,1′]-Bipiperidinyl-2,4-dione (2.00 g, 10.19 mmol) was dissolved in toluene (8 ml) and 2-chloro-4-fluorophenylamine (1.78 g, 12.23 mmol) was added. More toluene (5 ml) was added. The reaction mixture was boiled under reflux at 110° C. for 17 h then allowed to cool. When the reaction mixture reached rt the product precipitated and it was collected by filtration to yield a beige solid (1.80 g, 55%). to cool reached rt precipitated it was collected by filtration

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [1,1′]-Bipiperidinyl-2,4-dione (2.00 g, 10.19 mmol) was dissolved in toluene (8 ml) and 2-chloro-4-fluorophenylamine (1.78 g, 12.23 mmol) was added. More toluene (5 ml) was added. The reaction mixture was boiled under reflux at 110° C. for 17 h then allowed to cool. When the reaction mixture reached rt the product precipitated and it was collected by filtration to yield a beige solid (1.80 g, 55%). to cool reached rt precipitated it was collected by filtration

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

Procedure: A solution containing NH2OH.HCl (3.2 g, 46 mmol), anhydrous sodium sulphate (13 g, 93 mmol), and 2.2.2-trichloro-1-ethoxy ethanol (4.1 g, 21.2 mmol) in water (60 mL) was added to a solution of 2-chloro-4-fluroaniline (2 g, 0.27 mmol) in 4 M HCl (25 mL). The solution was refluxed for 40 minutes forming a white precipitate in the process. The mixture was cooled to room temperature, extracted with ethyl acetate three times, dried over sodium sulfate, filtered and concentrated in vacuo to provide 2.01 g of N-(2-chloro-4-fluoro-phenyl)-2-((E)-hydroxyimino)-acetamide: 1H NMR (300 MHz, CDCl3) δ 8.8 (bs, 1H), 8.4 (dd, 1H), 7.9 (s, 1H), 7.6 (s, 1H), 7.2 (dd, 1H), 7.0 (ddd, 1H). The solution was refluxed for 40 minutes forming a white precipitate in the process extracted with ethyl acetate three times dried over sodium sulfate filtered concentrated in vacuo

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

Procedure: A mixture of 35 g (240 mmole) 2-chloro-4-fluoroaniline, 37.7 g (240 mmole) of bromobenzene, 0.6 g (12 mmole) of palladium (II)acetate, 4.8 g (24 mmole) of tri-tert-butylphosphine, 46 g (480 mmole) of sodium tert-butoxide and o-xylene 800 ml were refluxed under nitrogen for about overnight. Then, the solution was filtered at 100° C. To receive the filtrate, And the o-xylene was removed under reduced pressure from the filtrate. The filtrate was extracted with 500 ml dichloromethane and 2000 ml water, the organic layer was dried with anhydrous magnesium sulfate, the solvent was removed and the residue was purified by column chromatography on silica (hexane-ethyl acetate) to give product 23.4 g (44%). were refluxed under nitrogen for about overnight Then, the solution was filtered at 100° C the o-xylene was removed under reduced pressure from the filtrate The filtrate was extracted with 500 ml dichloromethane and 2000 ml water the organic layer was dried with anhydrous magnesium sulfate the solvent was removed the residue was purified by column chromatography on silica (hexane-ethyl acetate)

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

Procedure: A solution of chloral hydrate (6.25 g, 37.8 mmol), sodium sulfate decahydrate (48.3 g, 340 mmol) and water (100 mL) was added to a stirred solution of 2-chloro-4-fluoroaniline (5.0 g, 34 mmol), hydroxylamine hydrochloride (9.19 g, 130 mmol), water (50 mL) and concentrated hydrochloric acid (3 mL). The reaction mixture was heated under reflux for 1 h, cooled to room temperature, stirred for 16 h and filtered. The filter-cake was recrystallised (methanol-water) to give the product (5.58 g, 75% yield) as a pale brown solid: IR νmax (Nujol)/cm−1 1655, 1613, 1536, 1267, 1191, 1021, 853 and 558; NMR δH (400 MHz, DMSO-d6) 7.20-7.29 (1H, m), 7.51-7.57 (1H, m), 7.78-7.84 (1H, m), 9.61 (1H, s) and 12.36 (1H, s). The reaction mixture was heated under reflux for 1 h filtered The filter-cake was recrystallised (methanol-water)