methyl 2-amino-4-fluorobenzoate

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.), stirred solution of 4-fluoro-2-aminobenzoic acid (2.68 g; 17.3 mmol) in dry tetrahydrofuran (60 mL) and MeOH (10 mL) was added a solution of trimethylsilyldiazomethane in hexanes (12 mL of 2.0 N; 24 mmol) via syringe over 20 minutes under nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 2 hours then concentrated in vacuo to provide the ester a light yellow solid (˜100%). to warm to room temperature then concentrated in vacuo

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

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

Procedure: Methyl 2-amino-4-fluorobenzoate (0.90 g), benzaldehyde (0.54 mL), sodium triacetoxyborohydride (1.58 g) and acetic acid (0.3 mL) in CH2Cl2 (20 mL) were stirred for 3 hours. The reaction was quenched with methanol, concentrated, and chromatographed on silica gel with 5% ethyl acetate/hexanes. The reaction was quenched with methanol concentrated chromatographed on silica gel with 5% ethyl acetate/hexanes

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.), stirred solution of 4-fluoro-2-aminobenzoic acid (2.68 g; 17.3 mmol) in dry tetrahydrofuran (60 mL) and MeOH (10 mL) was added a solution of trimethylsilyldiazomethane in hexanes (12 mL of 2.0 N; 24 mmol) via syringe over 20 minutes under nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 2 hours then concentrated in vacuo to provide the ester a light yellow solid (˜100%). to warm to room temperature then concentrated in vacuo

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

Procedure: Methyl 2-amino-4-fluorobenzoate (0.90 g), benzaldehyde (0.54 mL), sodium triacetoxyborohydride (1.58 g) and acetic acid (0.3 mL) in CH2Cl2 (20 mL) were stirred for 3 hours. The reaction was quenched with methanol, concentrated, and chromatographed on silica gel with 5% ethyl acetate/hexanes. The reaction was quenched with methanol concentrated chromatographed on silica gel with 5% ethyl acetate/hexanes

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.), stirred solution of 4-fluoro-2-aminobenzoic acid (2.68 g; 17.3 mmol) in dry tetrahydrofuran (60 mL) and MeOH (10 mL) was added a solution of trimethylsilyldiazomethane in hexanes (12 mL of 2.0 N; 24 mmol) via syringe over 20 minutes under nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 2 hours then concentrated in vacuo to provide the ester a light yellow solid (˜100%). to warm to room temperature then concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.), stirred solution of 4-fluoro-2-aminobenzoic acid (2.68 g; 17.3 mmol) in dry tetrahydrofuran (60 mL) and MeOH (10 mL) was added a solution of trimethylsilyldiazomethane in hexanes (12 mL of 2.0 N; 24 mmol) via syringe over 20 minutes under nitrogen atmosphere. The resulting solution was allowed to warm to room temperature and stirred for 2 hours then concentrated in vacuo to provide the ester a light yellow solid (˜100%). to warm to room temperature then concentrated in vacuo

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

Procedure: A stirred solution of 2-amino-4-fluorobenzoic acid (4.86 g, 31.3 mM) in anhydrous methanol (100 mL) was saturated with anhydrous hydrogen chloride and then refluxed for 4 days. During the reflux period, the reaction mixture was periodically resaturated with hydrogen chloride. After the reflux period, the reaction mixture was cooled and concentrated to leave a white solid. This material was dissolved in water and the resulting solution neutralized with aqueous sodium bicarbonate and extracted with diethyl ether. The combined extracts were dried (MgSO4), filtered and concentrated to leave (4.08 g, 80.6%) of the title compound as an off white solid, mp 66°-67° C.; MS(CI): 170 (M+H). refluxed for 4 days After the reflux period, the reaction mixture was cooled concentrated to leave a white solid extracted with diethyl ether The combined extracts were dried (MgSO4) filtered concentrated

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

Procedure: A stirred solution of 2-amino-4-fluorobenzoic acid (4.86 g, 31.3 mM) in anhydrous methanol (100 mL) was saturated with anhydrous hydrogen chloride and then refluxed for 4 days. During the reflux period, the reaction mixture was periodically resaturated with hydrogen chloride. After the reflux period, the reaction mixture was cooled and concentrated to leave a white solid. This material was dissolved in water and the resulting solution neutralized with aqueous sodium bicarbonate and extracted with diethyl ether. The combined extracts were dried (MgSO4), filtered and concentrated to leave (4.08 g, 80.6%) of the title compound as an off white solid, mp 66°-67° C.; MS(CI): 170 (M+H). refluxed for 4 days After the reflux period, the reaction mixture was cooled concentrated to leave a white solid extracted with diethyl ether The combined extracts were dried (MgSO4) filtered concentrated

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

Procedure: Methanesulphonyl chloride (0.68 g) was added dropwise to a stirred solution of methyl 4-fluoroanthranilate (1 g) in pyridine (dried over 4A sieves, 10 ml) at 0°-5°. After 18 hours at room temperature, the mixture was cooled to 0°-5° and further methanesulphonyl chloride (0.68 g) was added dropwise. The mixture was stirred for 24 hours at room temperature. Aqueous work up and recrystallisation from ethanol gave methyl N-(methylsulphonyl)-4-fluoroanthranilate, mp 115.5°-116.5°. (Compound 19). the mixture was cooled to 0°-5° Aqueous work up and recrystallisation from ethanol

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

Procedure: A stirred solution of 2-amino-4-fluorobenzoic acid (4.86 g, 31.3 mM) in anhydrous methanol (100 mL) was saturated with anhydrous hydrogen chloride and then refluxed for 4 days. During the reflux period, the reaction mixture was periodically resaturated with hydrogen chloride. After the reflux period, the reaction mixture was cooled and concentrated to leave a white solid. This material was dissolved in water and the resulting solution neutralized with aqueous sodium bicarbonate and extracted with diethyl ether. The combined extracts were dried (MgSO4), filtered and concentrated to leave (4.08 g, 80.6%) of the title compound as an off white solid, mp 66°-67° C.; MS(CI): 170 (M+H). refluxed for 4 days After the reflux period, the reaction mixture was cooled concentrated to leave a white solid extracted with diethyl ether The combined extracts were dried (MgSO4) filtered concentrated