methyl 2-chloro-5-fluorobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 2-chloro-5-fluorobenzoate (23, 35.0 g, 185.6 mmol) in dry THF (150 mL) was added NaBH4 (21.2 g, 557 mmol). Methanol (40 mL) was added dropwise at RT. After the addition, the mixture was stirred at RT for 1 h. Water (300 mL) was slowly added. The mixture was extracted with CH2Cl2 (200 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated to give (2-chloro-5-fluorophenyl)methanol (24). After the addition The mixture was extracted with CH2Cl2 (200 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-chloro-5-fluorobenzoic acid (22) (35.0 g, 200 mmol) in methanol (350 mL) was added cone. H2SO4 (5 mL). The mixture was heated at reflux for 24 h. Most of the solvent was evaporated, and the resulting mixture was diluted with water (300 mL). The mixture was extracted with EtOAc (150 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated to give methyl 2-chloro-5-fluorobenzoate (23). The mixture was heated at reflux for 24 h Most of the solvent was evaporated the resulting mixture was diluted with water (300 mL) The mixture was extracted with EtOAc (150 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4.00 g (20.6 mmol) 2-Chloro-5-fluoro-benzoic acid methyl ester (Rarechem) and 60 ml dimethylsulphoxid were added 2.03 g (24.7 mmol) dimethylamine hydrochloride and 5.97 g (43.2 mmol) potassium carbonate. The reaction mixture was stirred over night and was reduced with high vacuum rotation evaporator at 65° C. The residue was diluted with dichloromethane, washed twice with water. The combined water phases were extracted with dichloromethane. The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The oily crude product 18a was obtained in 99% yield (4.46 g, 20.9 mmol) and was used for the next step without purification. was reduced with high vacuum rotation evaporator at 65° C The residue was diluted with dichloromethane washed twice with water The combined water phases were extracted with dichloromethane The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution dried with sodium sulphate concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 4.00 g (20.6 mmol) 2-Chloro-5-fluoro-benzoic acid methyl ester (Rarechem) and 60 ml dimethylsulphoxid were added 2.03 g (24.7 mmol) dimethylamine hydrochloride and 5.97 g (43.2 mmol) potassium carbonate. The reaction mixture was stirred over night and was reduced with high vacuum rotation evaporator at 65° C. The residue was diluted with dichloromethane, washed twice with water. The combined water phases were extracted with dichloromethane. The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution, dried with sodium sulphate and concentrated. The oily crude product 18a was obtained in 99% yield (4.46 g, 20.9 mmol) and was used for the next step without purification. was reduced with high vacuum rotation evaporator at 65° C The residue was diluted with dichloromethane washed twice with water The combined water phases were extracted with dichloromethane The combined dichloromethane phases were washed with diluted sodium hydrogen carbonate solution dried with sodium sulphate concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 2-chloro-5-fluorobenzoate (23, 35.0 g, 185.6 mmol) in dry THF (150 mL) was added NaBH4 (21.2 g, 557 mmol). Methanol (40 mL) was added dropwise at RT. After the addition, the mixture was stirred at RT for 1 h. Water (300 mL) was slowly added. The mixture was extracted with CH2Cl2 (200 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated to give (2-chloro-5-fluorophenyl)methanol (24). After the addition The mixture was extracted with CH2Cl2 (200 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 2-chloro-5-fluorobenzoate (23, 35.0 g, 185.6 mmol) in dry THF (150 mL) was added NaBH4 (21.2 g, 557 mmol). Methanol (40 mL) was added dropwise at RT. After the addition, the mixture was stirred at RT for 1 h. Water (300 mL) was slowly added. The mixture was extracted with CH2Cl2 (200 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated to give (2-chloro-5-fluorophenyl)methanol (24). After the addition The mixture was extracted with CH2Cl2 (200 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-chloro-5-fluorobenzoic acid (22) (35.0 g, 200 mmol) in methanol (350 mL) was added cone. H2SO4 (5 mL). The mixture was heated at reflux for 24 h. Most of the solvent was evaporated, and the resulting mixture was diluted with water (300 mL). The mixture was extracted with EtOAc (150 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated to give methyl 2-chloro-5-fluorobenzoate (23). The mixture was heated at reflux for 24 h Most of the solvent was evaporated the resulting mixture was diluted with water (300 mL) The mixture was extracted with EtOAc (150 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methyl 2-chloro-5-fluorobenzoate (23, 35.0 g, 185.6 mmol) in dry THF (150 mL) was added NaBH4 (21.2 g, 557 mmol). Methanol (40 mL) was added dropwise at RT. After the addition, the mixture was stirred at RT for 1 h. Water (300 mL) was slowly added. The mixture was extracted with CH2Cl2 (200 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated to give (2-chloro-5-fluorophenyl)methanol (24). After the addition The mixture was extracted with CH2Cl2 (200 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-chloro-5-fluorobenzoic acid (22) (35.0 g, 200 mmol) in methanol (350 mL) was added cone. H2SO4 (5 mL). The mixture was heated at reflux for 24 h. Most of the solvent was evaporated, and the resulting mixture was diluted with water (300 mL). The mixture was extracted with EtOAc (150 mL×2). The combined extracts were washed with saturated NaHCO3 and brine, dried over MgSO4, and concentrated to give methyl 2-chloro-5-fluorobenzoate (23). The mixture was heated at reflux for 24 h Most of the solvent was evaporated the resulting mixture was diluted with water (300 mL) The mixture was extracted with EtOAc (150 mL×2) The combined extracts were washed with saturated NaHCO3 and brine dried over MgSO4 concentrated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of NaNO2 (3.69 g, 53.4 mmol in 50 mL water) was added dropwise to a stirred suspension of methyl 5-amino-2-chlorobenzoate (9 g, 48.5 mmol) in HCl (10%, 90 mL), keeping the temperature between 0-5° C. The reaction mixture was stirred for 10 min. and a solution of fluoroboric acid (70%, excess) was added to the mixture. The precipitate of diazonium fluoroborate salt was filtered, washed with water and dried. The pyrolysis of this salt was then carried out at 140° C. for 15-20 min. The residue was purified using a silica gel column and 10% CHCl3 in petroleum ether (60-80° C.) as an eluant to furnish the title compound. between 0-5° C The precipitate of diazonium fluoroborate salt was filtered washed with water dried The pyrolysis of this salt was then carried out at 140° C. for 15-20 min The residue was purified a silica gel column and 10% CHCl3 in petroleum ether (60-80° C.)