methyl 2,4,5-trifluorobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 30 ml tetrahydrofuran solution of 4.25 g (22.35 mmol) of methyl 2,4,5-trifluorobenzoate, 3.89 ml (22.35 mmol) of N-benzylpiperazine was added with ice cooling. The mixture was stirred at 0° C. for 0.5 hour, and at room temperature for 2.5 hours. Then, the reaction mixture was diluted with ethyl acetate, and the dilution was washed with water and a saturated aqueous solution of sodium chloride in this order. The washed system was dried over sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1) to obtain 2.61 g (34%) of the captioned compound. at room temperature for 2.5 hours the dilution was washed with water The washed system was dried over sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4,5-trifluorobenzoate (DSL Chemicals; 950.61 mg; 5 mmol; 1 eq.), sodium cyanide (306.30 mg; 6.25 mmol; 1.25 eq.) and tetrabutylammonium bromide (2 014.82 mg; 6.25 mmol; 1.25 eq.) were dissolved in DMF (10 mL). The resulting mixture was heated at 60° C. overnight. As the reaction was not complete, sodium cyanide (306.30 mg; 6.25 mmol; 1.25 eq.) was added and the mixture was stirred at 60° C. for additional 24 h. The resulting dark pink solution was diluted with EtOAc and washed with brine several times. It was dried over MgSO4, filtrated and evaporated, resulting into a sticky dark red oil, which was purified by flash chromatography (SiO2 100 g, EtOAc/c-hex 1:9 until 1:1), affording the title product. 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (dd, J=5.45, 8.41 Hz, 1H), 7.42 (dd, J=4.99, 8.88 Hz, 1H), 3.96 (s, 3H). LC/MS (Method A): 463.2 (M−H)−; 465.2 (M+H)+. HPLC (Method A) Rt 3.63 min (Purity: 99.9%). washed with brine several times It was dried over MgSO4 filtrated evaporated resulting into a sticky dark red oil, which was purified by flash chromatography (SiO2 100 g, EtOAc/c-hex 1:9 until 1:1)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4,5-trifluorobenzoate (DSL Chemicals; 950.61 mg; 5 mmol; 1 eq.), sodium cyanide (306.30 mg; 6.25 mmol; 1.25 eq.) and tetrabutylammonium bromide (2 014.82 mg; 6.25 mmol; 1.25 eq.) were dissolved in DMF (10 mL). The resulting mixture was heated at 60° C. overnight. As the reaction was not complete, sodium cyanide (306.30 mg; 6.25 mmol; 1.25 eq.) was added and the mixture was stirred at 60° C. for additional 24 h. The resulting dark pink solution was diluted with EtOAc and washed with brine several times. It was dried over MgSO4, filtrated and evaporated, resulting into a sticky dark red oil, which was purified by flash chromatography (SiO2 100 g, EtOAc/c-hex 1:9 until 1:1), affording the title product. 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (dd, J=5.45, 8.41 Hz, 1H), 7.42 (dd, J=4.99, 8.88 Hz, 1H), 3.96 (s, 3H). LC/MS (Method A): 463.2 (M−H)−; 465.2 (M+H)+. HPLC (Method A) Rt 3.63 min (Purity: 99.9%). washed with brine several times It was dried over MgSO4 filtrated evaporated resulting into a sticky dark red oil, which was purified by flash chromatography (SiO2 100 g, EtOAc/c-hex 1:9 until 1:1)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4,5-trifluorobenzoate (DSL Chemicals, 950 mg, 5 mmol), sodium cyanide (306 mg, 6.25 mmol) and tetrabutylammonium bromide (2.01 g, 6.25 mmol) were dissolved in DMF (10 mL) and the resulting mixture was heated at 60° C. overnight. Additional amount of sodium cyanide (306 mg, 6.25 mmol) was added and the mixture was stirred at 60° C. for 24 additional hours. The reaction mixture was diluted with EtOAc and washed with brine several times. The organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified by flash chromatography (silica, EtOAc/cHex) to give the title compound. 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (dd, J=8.4, 5.5 Hz, 1H), 7.42 (dd, J=8.9, 5.0 Hz, 1H), 3.96 (s, 3H). LC/MS (Method B): 463.2 (M−H)−, 465.2 (M+H)+. HPLC (Method A) Rt 3.63 min (Purity: 99.9%). washed with brine several times The organic layer was dried over MgSO4 concentrated under vacuum The residue was purified by flash chromatography (silica, EtOAc/cHex)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4,5-trifluorobenzoate (DSL Chemicals, 950 mg, 5 mmol), sodium cyanide (306 mg, 6.25 mmol) and tetrabutylammonium bromide (2.01 g, 6.25 mmol) were dissolved in DMF (10 mL) and the resulting mixture was heated at 60° C. overnight. Additional amount of sodium cyanide (306 mg, 6.25 mmol) was added and the mixture was stirred at 60° C. for 24 additional hours. The reaction mixture was diluted with EtOAc and washed with brine several times. The organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified by flash chromatography (silica, EtOAc/cHex) to give the title compound. 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (dd, J=8.4, 5.5 Hz, 1H), 7.42 (dd, J=8.9, 5.0 Hz, 1H), 3.96 (s, 3H). LC/MS (Method B): 463.2 (M−H)−, 465.2 (M+H)+. HPLC (Method A) Rt 3.63 min (Purity: 99.9%). washed with brine several times The organic layer was dried over MgSO4 concentrated under vacuum The residue was purified by flash chromatography (silica, EtOAc/cHex)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4,5-trifluorobenzoate (DSL Chemicals, 950 mg, 5 mmol), sodium cyanide (306 mg, 6.25 mmol) and tetrabutylammonium bromide (2.01 g, 6.25 mmol) were dissolved in DMF (10 mL) and the resulting mixture was heated at 60° C. overnight. Additional amount of sodium cyanide (306 mg, 6.25 mmol) was added and the mixture was stirred at 60° C. for 24 additional hours. The reaction mixture was diluted with EtOAc and washed with brine several times. The organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified by flash chromatography (silica, EtOAc/cHex) to give the title compound. 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (dd, J=8.4, 5.5 Hz, 1H), 7.42 (dd, J=8.9, 5.0 Hz, 1H), 3.96 (s, 3H). LC/MS (Method B): 463.2 (M−H)−, 465.2 (M+H)+. HPLC (Method A) Rt 3.63 min (Purity: 99.9%). washed with brine several times The organic layer was dried over MgSO4 concentrated under vacuum The residue was purified by flash chromatography (silica, EtOAc/cHex)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4,5-trifluorobenzoate (DSL Chemicals, 950 mg, 5 mmol), sodium cyanide (306 mg, 6.25 mmol) and tetrabutylammonium bromide (2.01 g, 6.25 mmol) were dissolved in DMF (10 mL) and the resulting mixture was heated at 60° C. overnight. Additional amount of sodium cyanide (306 mg, 6.25 mmol) was added and the mixture was stirred at 60° C. for 24 additional hours. The reaction mixture was diluted with EtOAc and washed with brine several times. The organic layer was dried over MgSO4 and concentrated under vacuum. The residue was purified by flash chromatography (silica, EtOAc/cHex) to give the title compound. 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (dd, J=8.4, 5.5 Hz, 1H), 7.42 (dd, J=8.9, 5.0 Hz, 1H), 3.96 (s, 3H). LC/MS (Method B): 463.2 (M−H)−, 465.2 (M+H)+. HPLC (Method A) Rt 3.63 min (Purity: 99.9%). washed with brine several times The organic layer was dried over MgSO4 concentrated under vacuum The residue was purified by flash chromatography (silica, EtOAc/cHex)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 30 ml tetrahydrofuran solution of 4.25 g (22.35 mmol) of methyl 2,4,5-trifluorobenzoate, 3.89 ml (22.35 mmol) of N-benzylpiperazine was added with ice cooling. The mixture was stirred at 0° C. for 0.5 hour, and at room temperature for 2.5 hours. Then, the reaction mixture was diluted with ethyl acetate, and the dilution was washed with water and a saturated aqueous solution of sodium chloride in this order. The washed system was dried over sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1) to obtain 2.61 g (34%) of the captioned compound. at room temperature for 2.5 hours the dilution was washed with water The washed system was dried over sodium sulfate the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate=2/1)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2,4,5-trifluorobenzoate (DSL Chemicals; 950.61 mg; 5 mmol; 1 eq.), sodium cyanide (306.30 mg; 6.25 mmol; 1.25 eq.) and tetrabutylammonium bromide (2 014.82 mg; 6.25 mmol; 1.25 eq.) were dissolved in DMF (10 mL). The resulting mixture was heated at 60° C. overnight. As the reaction was not complete, sodium cyanide (306.30 mg; 6.25 mmol; 1.25 eq.) was added and the mixture was stirred at 60° C. for additional 24 h. The resulting dark pink solution was diluted with EtOAc and washed with brine several times. It was dried over MgSO4, filtrated and evaporated, resulting into a sticky dark red oil, which was purified by flash chromatography (SiO2 100 g, EtOAc/c-hex 1:9 until 1:1), affording the title product. 1H NMR (DMSO-d6, 300 MHz) δ 7.77 (dd, J=5.45, 8.41 Hz, 1H), 7.42 (dd, J=4.99, 8.88 Hz, 1H), 3.96 (s, 3H). LC/MS (Method A): 463.2 (M−H)−; 465.2 (M+H)+. HPLC (Method A) Rt 3.63 min (Purity: 99.9%). washed with brine several times It was dried over MgSO4 filtrated evaporated resulting into a sticky dark red oil, which was purified by flash chromatography (SiO2 100 g, EtOAc/c-hex 1:9 until 1:1)