methyl 5-amino-2-(trifluoromethoxy)benzoate

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

Procedure: 5-Amino-2-trifluoromethoxybenzoic acid methyl ester (3.0 g, 12.8 mmol) was dissolved in THF (20 mL) in a three-necked flask equipped with a thermometer and an addition funnel under nitrogen. Under stirring and ice-cooling lithium aluminum hydride (1 M in THF, 15 mL) was added dropwise within 10 minutes. Stirring was continued at room temperature for 1 hr, and the reaction was concentrated in vacuo. The residue was suspended in DCM (150 mL) and water (50 mL), then filtered through celite, washed with DCM and water. The filtrate was separated, and the water phase was extracted once more with DCM (30 mL). The combined organic phases were washed with water (2×20 mL), dried (magnesium sulphate) and concentrated in vacuo to give 2.47 g of (5-amino-2-trifluoromethoxyphenyl)methanol. equipped with a thermometer and an addition funnel under nitrogen was added dropwise within 10 minutes Stirring the reaction was concentrated in vacuo water (50 mL), then filtered through celite washed with DCM and water The filtrate was separated the water phase was extracted once more with DCM (30 mL) The combined organic phases were washed with water (2×20 mL) dried (magnesium sulphate) concentrated in vacuo

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Nitro-2-trifluoromethoxybenzoic acid methyl ester (5.69 g, 21.5 mmol) was dissolved in ethanol 99.9% (80 mL) and stannous (II) chloride dihydrate (24.2 g, 107 mmol) was added. The suspension was stirred on an oil-bath at 75° C for 2 hours and concentrated in vacuo. Ethyl acetate (100 mL) and water (50 mL) was added and pH was adjusted to pH 8 with 4 N sodium hydroxide (50 mL). The liquid was decanted from the precipitation. The precipitate was washed twice with ethyl acetate. The aqueous phase was extracted twice with ethyl acetate (60 mL). The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL), dried (magnesium sulphate) and concentrated in vacuo. Purification by column chromatography (120 g silica) using ethyl acetate and heptane (1:1) as eluent afforded 3.8 g of 5-amino-2-trifluoromethoxybenzoic acid methyl ester. concentrated in vacuo Ethyl acetate (100 mL) and water (50 mL) was added The liquid was decanted from the precipitation The precipitate was washed twice with ethyl acetate The aqueous phase was extracted twice with ethyl acetate (60 mL) The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL) dried (magnesium sulphate) concentrated in vacuo Purification by column chromatography (120 g silica)

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

Procedure: 5-Amino-2-trifluoromethoxybenzoic acid methyl ester (3.0 g, 12.8 mmol) was dissolved under nitrogen in THF (20 mL) in a three-necked flask equipped with a thermometer and a separatory funnel. With stirring and ice-cooling lithium aluminium hydride (1 M in THF, 15 mL) was added dropwise over 10 min. Stirring was continued at room temperature for 1 hour, and the reaction mixture was concentrated in vacuo. The residue was suspended in DCM (150 mL) and water (50 mL), and filtered through celite. The filtrate was partitioned between DCM and water. The combined organic phases were washed with water (2×20 mL), dried (magnesium sulphate) and concentrated in vacuo to give 2.47 g of (5-amino-2-trifluoromethoxy-phenyl)methanol equipped with a thermometer and a separatory funnel was added dropwise over 10 min Stirring the reaction mixture was concentrated in vacuo water (50 mL), and filtered through celite The filtrate was partitioned between DCM and water The combined organic phases were washed with water (2×20 mL) dried (magnesium sulphate) concentrated in vacuo

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Nitro-2-trifluoromethoxybenzoic acid methyl ester (5.69 g, 21.5 mmol) was dissolved in ethanol 99.9% (80 mL) and added stannous(II)chloride dihydrate (24.2 g, 107 mmol). The suspension was stirred at 75° C. for 2 hours and then concentrated in vacuo. The residue was added ethyl acetate (100 mL) and water (50 mL) and pH was adjusted to pH 8 with 4 N sodium hydroxide (50 mL). The liquid was decanted from the fine precipitation, which occurred, and the precipitate was washed with ethyl acetate and decanted twice. The combine organic phases were washed with water:saturated sodium chloride (1:1) solution (2×100 mL), dried (magnesium sulphate) and concentrated in vacuo. The residue was purified by column chromatography (120 g silica) using ethyl acetate:heptane (1:1) as eluent to give 3.8 g of 5-amino-2-trifluoromethoxybenzoic acid methyl ester. concentrated in vacuo The residue was added ethyl acetate (100 mL) and water (50 mL) and pH The liquid was decanted from the fine precipitation, which the precipitate was washed with ethyl acetate decanted twice The combine organic phases were washed with water saturated sodium chloride (1:1) solution (2×100 mL), dried (magnesium sulphate) concentrated in vacuo The residue was purified by column chromatography (120 g silica)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Nitro-2-trifluoromethoxybenzoic acid methyl ester (5.69 g, 21.5 mmol) was dissolved in ethanol 99.9% (80 mL) and stannous (II) chloride dihydrate (24.2 g, 107 mmol) was added. The suspension was stirred on an oil-bath at 75° C. for 2 hours and concentrated in vacuo. Ethyl acetate (100 mL) and water (50 mL) was added and pH was adjusted to pH 8 with 4 N sodium hydroxide (50 mL). The liquid was decanted from the precipitation. The precipitate was washed twice with ethyl acetate. The aqueous phase was extracted twice with ethyl acetate (60 mL). The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL), dried (magnesium sulphate) and concentrated in vacuo. Purification by column chromatography (120 g silica) using ethyl acetate and heptane (1:1) as eluent afforded 3.8 g of 5-amino-2-trifluoromethoxybenzoic acid methyl ester. concentrated in vacuo Ethyl acetate (100 mL) and water (50 mL) was added The liquid was decanted from the precipitation The precipitate was washed twice with ethyl acetate The aqueous phase was extracted twice with ethyl acetate (60 mL) The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL) dried (magnesium sulphate) concentrated in vacuo Purification by column chromatography (120 g silica)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Nitro-2-trifluoromethoxybenzoic acid methyl ester (5.69 g, 21.5 mmol) was dissolved in ethanol 99.9% (80 mL) and stannous (II) chloride dihydrate (24.2 g, 107 mmol) was added. The suspension was stirred on an oil-bath at 75° C. for 2 hours and concentrated in vacuo. Ethyl acetate (100 mL) and water (50 mL) was added and pH was adjusted to pH 8 with 4 N sodium hydroxide (50 mL). The liquid was decanted from the precipitation. The precipitate was washed twice with ethyl acetate. The aqueous phase was extracted twice with ethyl acetate (60 mL). The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL), dried (magnesium sulphate) and concentrated in vacuo. Purification by column chromatography (120 g silica) using ethyl acetate and heptane (1:1) as eluent afforded 3.8 g of 5-amino-2-trifluoromethoxybenzoic acid methyl ester. concentrated in vacuo Ethyl acetate (100 mL) and water (50 mL) was added The liquid was decanted from the precipitation The precipitate was washed twice with ethyl acetate The aqueous phase was extracted twice with ethyl acetate (60 mL) The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL) dried (magnesium sulphate) concentrated in vacuo Purification by column chromatography (120 g silica)

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

Procedure: 5-Amino-2-trifluoromethoxybenzoic acid methyl ester (3.0 g, 12.8 mmol) was dissolved under nitrogen in THF (20 mL) in a three-necked flask equipped with a thermometer and a separatory funnel. With stirring and ice-cooling lithium aluminium hydride (1 M in THF, 15 mL) was added dropwise over 10 min. Stirring was continued at room temperature for 1 hour, and the reaction mixture was concentrated in vacuo. The residue was suspended in DCM (150 mL) and water (50 mL), and filtered through celite. The filtrate was partitioned between DCM and water. The combined organic phases were washed with water (2×20 mL), dried (magnesium sulphate) and concentrated in vacuo to give 2.47 g of (5-amino-2-trifluoromethoxyphenyl)methanol. equipped with a thermometer and a separatory funnel was added dropwise over 10 min Stirring the reaction mixture was concentrated in vacuo water (50 mL), and filtered through celite The filtrate was partitioned between DCM and water The combined organic phases were washed with water (2×20 mL) dried (magnesium sulphate) concentrated in vacuo

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Nitro-2-trifluoromethoxybenzoic acid methyl ester (5.69 g, 21.5 mmol) was dissolved in ethanol 99.9% (80 mL) and added stannous(II)chloride dihydrate (24.2 g, 107 mmol). The suspension was stirred at 75° C. for 2 hours and then concentrated in vacuo. The residue was added ethyl acetate (100 mL) and water (50 mL) and pH was adjusted to pH 8 with 4 N sodium hydroxide (50 mL). The liquid was decanted from the fine precipitation, which occurred, and the precipitation was washed with ethyl acetate and decanted twice. The combined organic phases were washed with water saturated sodium chloride (1:1) solution (2×100 mL), dried (magnesium sulphate) and concentrated in vacuo. The residue was purified by column chromatography (120 g silica) using ethyl acetate:heptane (1:1) as eluent to give 3.8 g of 5-amino-2-trifluoromethoxybenzoic acid methyl ester. concentrated in vacuo The residue was added ethyl acetate (100 mL) and water (50 mL) and pH The liquid was decanted from the fine precipitation, which the precipitation was washed with ethyl acetate decanted twice The combined organic phases were washed with water saturated sodium chloride (1:1) solution (2×100 mL) dried (magnesium sulphate) concentrated in vacuo The residue was purified by column chromatography (120 g silica)

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Nitro-2-trifluoromethoxybenzoic acid methyl ester (5.69 g, 21.5 mmol) was dissolved in ethanol 99.9% (80 mL) and added stannous(II)chloride dihydrate (24.2 g, 107 mmol). The suspension was stirred at 75° C. for 2 hours and then concentrated in vacuo. The residue was added ethyl acetate (100 mL) and water (50 mL) and pH was adjusted to pH 8 with 4 N sodium hydroxide (50 mL). The liquid was decanted from the fine precipitation, which occurred, and the precipitation was washed with ethyl acetate and decanted twice. The combined organic phases were washed with water saturated sodium chloride (1:1) solution (2×100 mL), dried (magnesium sulphate) and concentrated in vacuo. The residue was purified by column chromatography (120 g silica) using ethyl acetate:heptane (1:1) as eluent to give 3.8 g of 5-amino-2-trifluoromethoxybenzoic acid methyl ester. concentrated in vacuo The residue was added ethyl acetate (100 mL) and water (50 mL) and pH The liquid was decanted from the fine precipitation, which the precipitation was washed with ethyl acetate decanted twice The combined organic phases were washed with water saturated sodium chloride (1:1) solution (2×100 mL) dried (magnesium sulphate) concentrated in vacuo The residue was purified by column chromatography (120 g silica)

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

Procedure: 5-Amino-2-trifluoromethoxybenzoic acid methyl ester (3.0 g, 12.8 mmol) was dissolved in THF (20 mL) in a three-necked flask equipped with a thermometer and an addition funnel under nitrogen. Under stirring and ice-cooling lithium aluminum hydride (1 M in THF, 15 mL) was added dropwise within 10 minutes. Stirring was continued at room temperature for 1 hr, and the reaction was concentrated in vacuo. The residue was suspended in DCM (150 mL) and water (50 mL), then filtered through celite, washed with DCM and water. The filtrate was separated, and the water phase was extracted once more with DCM (30 mL). The combined organic phases were washed with water (2×20 mL), dried (magnesium sulphate) and concentrated in vacuo to give 2.47 g of (5-amino-2-trifluoromethoxyphenyl)methanol. equipped with a thermometer and an addition funnel under nitrogen was added dropwise within 10 minutes Stirring the reaction was concentrated in vacuo water (50 mL), then filtered through celite washed with DCM and water The filtrate was separated the water phase was extracted once more with DCM (30 mL) The combined organic phases were washed with water (2×20 mL) dried (magnesium sulphate) concentrated in vacuo

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

Procedure: 5-Amino-2-trifluoromethoxybenzoic acid methyl ester (3.0 g, 12.8 mmol) was dissolved in THF (20 mL) in a three-necked flask equipped with a thermometer and an addition funnel under nitrogen. Under stirring and ice-cooling lithium aluminum hydride (1 M in THF, 15 mL) was added dropwise within 10 minutes. Stirring was continued at room temperature for 1 hr, and the reaction was concentrated in vacuo. The residue was suspended in DCM (150 mL) and water (50 mL), then filtered through celite, washed with DCM and water. The filtrate was separated, and the water phase was extracted once more with DCM (30 mL). The combined organic phases were washed with water (2×20 mL), dried (magnesium sulphate) and concentrated in vacuo to give 2.47 g of (5-amino-2-trifluoromethoxyphenyl)methanol. equipped with a thermometer and an addition funnel under nitrogen was added dropwise within 10 minutes Stirring the reaction was concentrated in vacuo water (50 mL), then filtered through celite washed with DCM and water The filtrate was separated the water phase was extracted once more with DCM (30 mL) The combined organic phases were washed with water (2×20 mL) dried (magnesium sulphate) concentrated in vacuo

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Nitro-2-trifluoromethoxybenzoic acid methyl ester (5.69 g, 21.5 mmol) was dissolved in ethanol 99.9% (80 mL) and stannous (II) chloride dihydrate (24.2 g, 107 mmol) was added. The suspension was stirred on an oil-bath at 75° C for 2 hours and concentrated in vacuo. Ethyl acetate (100 mL) and water (50 mL) was added and pH was adjusted to pH 8 with 4 N sodium hydroxide (50 mL). The liquid was decanted from the precipitation. The precipitate was washed twice with ethyl acetate. The aqueous phase was extracted twice with ethyl acetate (60 mL). The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL), dried (magnesium sulphate) and concentrated in vacuo. Purification by column chromatography (120 g silica) using ethyl acetate and heptane (1:1) as eluent afforded 3.8 g of 5-amino-2-trifluoromethoxybenzoic acid methyl ester. concentrated in vacuo Ethyl acetate (100 mL) and water (50 mL) was added The liquid was decanted from the precipitation The precipitate was washed twice with ethyl acetate The aqueous phase was extracted twice with ethyl acetate (60 mL) The combined organic phases were washed with a saturated sodium chloride solution (2×100 mL) dried (magnesium sulphate) concentrated in vacuo Purification by column chromatography (120 g silica)