1-(5-amino-2-fluorophenyl)ethanone

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.4 g (152 mmol) of 2-fluoro-5-nitroacetophenone, 343 g (1.52 mol) of tin chloride dihydrate and 250 ml of ethyl acetate are introduced into a 1-liter three-necked flask. The reaction mixture is heated to 70° C. for 30 minutes and then poured onto 1 liter of crushed ice, 30% sodium hydroxide solution is added and the mixture is extracted with 3 times 350 ml of ethyl acetate. The organic phases are combined, dried over magnesium sulphate and concentrated. 11.26 g of product are obtained in the form of an oil. is added the mixture is extracted with 3 times 350 ml of ethyl acetate dried over magnesium sulphate concentrated

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

Procedure: Benzyl chloroformate (3 mL, 21.5 mmol) was added to a mixture of 1-(5-amino-2-fluorophenyl)ethanone (3 g, 19.6 mmol) and tetrabutylammonium bromide at room temperature. The reaction was stirred at room temperature for 24 hours, the crude was treated with AcOEt (50 mL) and H2O (50 mL), the organic phase was separated and evaporated in vacuo. The crude was purified by column chromatography (silica gel; MeOH/DCM). The desired fractions were collected and the solvents evaporated in vacuo to afford intermediate A40 as a cream solid (4.7 g, 84%). LCMS: 286 [M−H]−; Rt: 2.81 min (method 3). the organic phase was separated evaporated in vacuo The crude was purified by column chromatography (silica gel; MeOH/DCM) The desired fractions were collected the solvents evaporated in vacuo

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

Procedure: Benzyl chloroformate (3 mL, 21.5 mmol) was added to a mixture of 1-(5-amino-2-fluorophenyl)ethanone (3 g, 19.6 mmol) and tetrabutylammonium bromide at room temperature. The reaction was stirred at room temperature for 24 hours, the crude was treated with AcOEt (50 mL) and H2O (50 mL), the organic phase was separated and evaporated in vacuo. The crude was purified by column chromatography (silica gel; MeOH/DCM). The desired fractions were collected and the solvents evaporated in vacuo to afford intermediate A40 as a cream solid (4.7 g, 84%). LCMS: 286 [M−H]−; Rt: 2.81 min (method 3). the organic phase was separated evaporated in vacuo The crude was purified by column chromatography (silica gel; MeOH/DCM) The desired fractions were collected the solvents evaporated in vacuo

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.4 g (152 mmol) of 2-fluoro-5-nitroacetophenone, 343 g (1.52 mol) of tin chloride dihydrate and 250 ml of ethyl acetate are introduced into a 1-liter three-necked flask. The reaction mixture is heated to 70° C. for 30 minutes and then poured onto 1 liter of crushed ice, 30% sodium hydroxide solution is added and the mixture is extracted with 3 times 350 ml of ethyl acetate. The organic phases are combined, dried over magnesium sulphate and concentrated. 11.26 g of product are obtained in the form of an oil. is added the mixture is extracted with 3 times 350 ml of ethyl acetate dried over magnesium sulphate concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.4 g (152 mmol) of 2-fluoro-5-nitroacetophenone, 343 g (1.52 mol) of tin chloride dihydrate and 250 ml of ethyl acetate are introduced into a 1-liter three-necked flask. The reaction mixture is heated to 70° C. for 30 minutes and then poured onto 1 liter of crushed ice, 30% sodium hydroxide solution is added and the mixture is extracted with 3 times 350 ml of ethyl acetate. The organic phases are combined, dried over magnesium sulphate and concentrated. 11.26 g of product are obtained in the form of an oil. is added the mixture is extracted with 3 times 350 ml of ethyl acetate dried over magnesium sulphate concentrated

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

Procedure: To a solution of 1.19 g (7.77 mmol) of 1-(5-amino-2-fluorophenyl)ethanone in 18 ml of dry tetrahydrofuran at room temperature under an atmosphere of nitrogen was added 1.86 g (8.54 mol) of tert-butyl dicarbonate. The solution was stirred for 28 hours at room temperature followed by 17 hours at 45° C., cooled to room temperature and evaporated under reduced pressure. The residue was dissolved in ethyl acetate and the solution washed with sodium bicarbonate solution, dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol 4:1 for the elution. There was obtained 1.45 g of (3-acetyl-4-fluorophenyl)carbamic acid tert-butyl ester MS: m/e 271 [M+CH3CN]+. followed by 17 hours at 45° C. cooled to room temperature evaporated under reduced pressure The residue was dissolved in ethyl acetate the solution washed with sodium bicarbonate solution dried over magnesium sulphate evaporated to dryness the residue chromatographed on silica gel for the elution

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

Procedure: To a solution of 1.19 g (7.77 mmol) of 1-(5-amino-2-fluorophenyl)ethanone in 18 ml of dry tetrahydrofuran at room temperature under an atmosphere of nitrogen was added 1.86 g (8.54 mol) of tert-butyl dicarbonate. The solution was stirred for 28 hours at room temperature followed by 17 hours at 45° C., cooled to room temperature and evaporated under reduced pressure. The residue was dissolved in ethyl acetate and the solution washed with sodium bicarbonate solution, dried over magnesium sulphate, evaporated to dryness and the residue chromatographed on silica gel using ethyl acetate/petrol 4:1 for the elution. There was obtained 1.45 g of (3-acetyl-4-fluorophenyl)carbamic acid tert-butyl ester MS: m/e 271 [M+CH3CN]+. followed by 17 hours at 45° C. cooled to room temperature evaporated under reduced pressure The residue was dissolved in ethyl acetate the solution washed with sodium bicarbonate solution dried over magnesium sulphate evaporated to dryness the residue chromatographed on silica gel for the elution

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

Procedure: 5'-Amino-2'-fluoroacetophenone (28 g) was dissolved in a mixture of 100 ml of ethyl acetate and 15.9 g of pyridine, a solution of 23 g of methanesulfonyl chloride in 50 ml of ethyl acetate was added with ice-cooling and stirring and the mixture was made to react at room temperature for 3 hours. The reaction mixture was washed with water, dried, the solvent was evaporated therefrom and the residue was purified by silica gel column chromatography (eluting with chloroform) to give 33.7 g of 3'-acetyl-4'-fluoromethanesulfonanilide, m.p. 120°-123° C. cooling to react at room temperature for 3 hours The reaction mixture was washed with water dried the solvent was evaporated the residue was purified by silica gel column chromatography (eluting with chloroform)

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

Procedure: 5'-Amino-2'-fluoroacetophenone (28 g) was dissolved in a mixture of 100 ml of ethyl acetate and 15.9 g of pyridine, a solution of 23 g of methanesulfonyl chloride in 50 ml of ethyl acetate was added with ice-cooling and stirring and the mixture was made to react at room temperature for 3 hours. The reaction mixture was washed with water, dried, the solvent was evaporated therefrom and the residue was purified by silica gel column chromatography (eluting with chloroform) to give 33.7 g of 3'-acetyl-4'-fluoromethanesulfonanilide, m.p. 120°-123° C. cooling to react at room temperature for 3 hours The reaction mixture was washed with water dried the solvent was evaporated the residue was purified by silica gel column chromatography (eluting with chloroform)

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

Procedure: 5'-Amino-2'-fluoroacetophenone (28 g) was dissolved in a mixture of 100 ml of ethyl acetate and 15.9 g of pyridine, a solution of 23 g of methanesulfonyl chloride in 50 ml of ethyl acetate was added with ice-cooling and stirring and the mixture was made to react at room temperature for 3 hours. The reaction mixture was washed with water, dried, the solvent was evaporated therefrom and the residue was purified by silica gel column chromatography (eluting with chloroform) to give 33.7 g of 3'-acetyl-4'-fluoromethanesulfonanilide, m.p. 120°-123° C. cooling to react at room temperature for 3 hours The reaction mixture was washed with water dried the solvent was evaporated the residue was purified by silica gel column chromatography (eluting with chloroform)

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

Procedure: A mixture of 1-(5-amino-2-fluoro-phenyl)-ethanone (3.5 g), bromoethyl ether (5.929 g), and i-Pr2NEt (7.121 g) in toluene (20 mL) was refluxed for 16 hours. After cooling, the reaction mixture was quenched with water. The aqueous layer was extracted with dichloromethane, and the combined organic layers were dried over magnesium sulphate, filtered, and concentrated in vacuo. The residue was purified by silica gel flash chromatography (25% ethyl acetate in hexane) to give 3.74 g of the title compound as an oil. was refluxed for 16 hours After cooling the reaction mixture was quenched with water The aqueous layer was extracted with dichloromethane the combined organic layers were dried over magnesium sulphate filtered concentrated in vacuo The residue was purified by silica gel flash chromatography (25% ethyl acetate in hexane)

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

Procedure: A mixture of 1-(2-fluoro-5-nitro-phenyl)ethanone (7.3 g) and 5% Pt(S)/C (730 mg) in ethanol (50 mL) was hydrogenated at 50 psi for 20 hours. The reaction mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was purified by silica gel flash chromatography (33% ethyl acetate in hexane) to give the title compound as a solid (3.56 g). The reaction mixture was filtered through Celite the filtrate was concentrated in vacuo The residue was purified by silica gel flash chromatography (33% ethyl acetate in hexane)