ethyl 3-amino-4-fluorobenzoate

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

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

Procedure: To a solution of ethyl 3-amino-4-fluorobenzoate (5.47 g, 30 mmol) and pyridine (2.55 mL, 33 mmol) in DCM (150 mL) was added 2,6-difluorobenzenesulfonyl chloride (4.45 mL, 33 mmol). The reaction was stirred overnight at rt. After 16 h, the reaction mixture was concentrated, triturated with ether, and dried in vacuo to generate 7.87 g (66% yield) of the product of Step A as a white powder. MS (ESI): 360 (M+H). After 16 h the reaction mixture was concentrated triturated with ether dried in vacuo

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

Procedure: The titled compound was prepared following the procedure A using 4-[(4-butylphenyl)ethenyl]benzaldehyde and ethyl 3-amino-4-fluorobenzoate as a pale yellow oil (61%). 1H NMR (CDCl3, 300 MHz) δ 7.49 (d, J=8.3 Hz, 2H), 7.42 (d, J=7.9 Hz, 2H), 7.35 (m, 4H), 7.14 (d, J=7.9 Hz, 2H), 7.00 (dd, J=11.0, 8.7 Hz, 1H), 4.41 (brs, 2H), 4.30 (q, J=7.2 Hz, 2H), 2.60 (t, J=7.7 Hz, 2H), 1.69-1.53 (m, 4H), 1.34 (t, J=7.2 Hz, 3H), 0.91 (t, J=7.4 Hz, 3H). HPLC, Rt: 5.87 min (Purity: 94.3%).

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

Procedure: The titled compound was prepared following the procedure A using 4-[(4-butylphenyl)ethenyl]benzaldehyde and ethyl 3-amino-4-fluorobenzoate as a pale yellow oil (61%). 1H NMR (CDCl3, 300 MHz) δ 7.49 (d, J=8.3 Hz, 2H), 7.42 (d, J=7.9 Hz, 2H), 7.35 (m, 4H), 7.14 (d, J=7.9 Hz, 2H), 7.00 (dd, J=11.0, 8.7 Hz, 1H), 4.41 (brs, 2H), 4.30 (q, J=7.2 Hz, 2H), 2.60 (t, J=7.7 Hz, 2H), 1.69-1.53 (m, 4H), 1.34 (t, J=7.2 Hz, 3H), 0.91 (t, J=7.4 Hz, 3H). HPLC, Rt: 5.87 min (Purity: 94.3%).

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

Procedure: To a solution of ethyl 3-amino-4-fluorobenzoate (5.47 g, 30 mmol) and pyridine (2.55 mL, 33 mmol) in DCM (150 mL) was added 2,6-difluorobenzenesulfonyl chloride (4.45 mL, 33 mmol). The reaction was stirred overnight at rt. After 16 h, the reaction mixture was concentrated, triturated with ether, and dried in vacuo to generate 7.87 g (66% yield) of the product of Step A as a white powder. MS (ESI): 360 (M+H). After 16 h the reaction mixture was concentrated triturated with ether dried in vacuo

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

Procedure: To a solution of ethyl 3-amino-4-fluorobenzoate (5.47 g, 30 mmol) and pyridine (2.55 mL, 33 mmol) in DCM (150 mL) was added 2,6-difluorobenzenesulfonyl chloride (4.45 mL, 33 mmol). The reaction was stirred overnight at rt. After 16 h, the reaction mixture was concentrated, triturated with ether, and dried in vacuo to generate 7.87 g (66% yield) of the product of Step A as a white powder. MS (ESI): 360 (M+H). After 16 h the reaction mixture was concentrated triturated with ether dried in vacuo

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

Procedure: A solution of 2.8 g (15.3 mmol) of ethyl 3-amino-4-fluorobenzoate (cf L. S. Fosdick and A. F. Dodds in J. Amer. Chem. Soc. 65, 2305 (1943)) and 1.56 mL (1.85 g=17.0 mmol) of methoxyacetylchloride in 50 mL chlorobenzene was stirred for 1 hour at 50° C. and then refluxed for 15 minutes. Then the solvent was distilled off in vacuo and the crude product obtained was purified by flash chromatography (silica gel; dichloromethane/ethanol=100:1). The desired compound, initially oily, solidified within a few days. Yield: 3.8 g (98% of theory); Rf value: 0.38 (silica gel; dichloromethane/ethanol=19:1). refluxed for 15 minutes Then the solvent was distilled off in vacuo

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

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

Procedure: A solution of 2.8 g (15.3 mmol) of ethyl 3-amino-4-fluorobenzoate (cf L. S. Fosdick and A. F. Dodds in J. Amer. Chem. Soc. 65, 2305 (1943)) and 1.56 mL (1.85 g=17.0 mmol) of methoxyacetylchloride in 50 mL chlorobenzene was stirred for 1 hour at 50° C. and then refluxed for 15 minutes. Then the solvent was distilled off in vacuo and the crude product obtained was purified by flash chromatography (silica gel; dichloromethane/ethanol=100:1). The desired compound, initially oily, solidified within a few days. Yield: 3.8 g (98% of theory); Rf value: 0.38 (silica gel; dichloromethane/ethanol=19:1). refluxed for 15 minutes Then the solvent was distilled off in vacuo

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

Procedure: A solution of 2.8 g (15.3 mMol) of ethyl 3-amino-4-fluoro-benzoate (cf. L. S. Fosdick, A. F. Dodds in J. Amer. Chem. Soc. 65, 2305 (1943)) and 1.56 ml (1.85 g=17.0 mMol) of methoxyacetylchloride in 50 ml chlorobenzene was stirred for 1 hour at 50° C. and then refluxed for 15 minutes. Then the solvent was distilled off in vacuo and the crude product obtained was purified by flash chromatography (silica gel; dichloromethane/ethanol=100:1). The desired compound, initially oily, solidified within a few days. Yield: 3.8 g (98% of theory), Rf value: 0.38 (silica gel; dichloromethane/ethanol=19:1) refluxed for 15 minutes Then the solvent was distilled off in vacuo

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

Procedure: To a solution of ethyl 3-amino-4-fluorobenzoate (5.47 g, 30 mmol) and pyridine (2.55 mL, 33 mmol) in DCM (150 mL) was added 2,6-difluorobenzenesulfonyl chloride (4.45 mL, 33 mmol). The reaction was stirred overnight at rt. After 16 h, the reaction mixture was concentrated, triturated with ether, and dried in vacuo to generate 7.87 g (66% yield) of the product of Step A as a white powder. MS (ESI): 360 (M+H). After 16 h the reaction mixture was concentrated triturated with ether dried in vacuo

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

Procedure: To a solution of ethyl 3-amino-4-fluorobenzoate (5.47 g, 30 mmol) and pyridine (2.55 mL, 33 mmol) in DCM (150 mL) was added 2,6-difluorobenzenesulfonyl chloride (4.45 mL, 33 mmol). The reaction was stirred overnight at rt. After 16 h, the reaction mixture was concentrated, triturated with ether, and dried in vacuo to generate 7.87 g (66% yield) of the product of Step A as a white powder. MS (ESI): 360 (M+H). After 16 h the reaction mixture was concentrated triturated with ether dried in vacuo