methyl 2-(cyanomethyl)benzoate

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

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

Procedure: With gentle heating, 175 g (1.08 mol) of 2-cyanomethyl-benzoic acid (for preparation see: Org. Synthesis, Coll, Vol. 3,174) are dissolved in 1.7 liters of CH2Cl2; 242 ml (=90%, 1.6 mol) of dimethylformamide dimethylacetal are added dropwise at room temperature, and stirring is carried out for 38 hours to complete the reaction. The reaction mixture is washed with 2×1.2 liters of saturated NaHCO3 solution and brine. The aqueous phases are extracted using 2 portions of CH2Cl2, and the organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2; ethyl acetate/hexane 1:4, applied in ethyl acetate/hexane/CH2Cl2) yields the title compound: m.p. 49-50° C.; 1H NMR (DMSO-d6) 7.96 (d, 1H), 7.66 (t, 1H), 7.57 (d, 1H), 7.51 (t, 1H), 4.26 (s, 2H), 3.86 (s, 3H); Anal. calc. (C10H9NO2) C 68.56%, H 5.18%, N 8.00%; found C 68.5%, H 5.1%, N 7.9%. the reaction The reaction mixture is washed with 2×1.2 liters of saturated NaHCO3 solution and brine The aqueous phases are extracted the organic phases are dried (Na2SO4) concentrated by evaporation

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

Procedure: To a solution of 1.85 g of potassium t-butoxide in 32.3 ml of a dry tetrahydrofuran was added 2.83 g of methyl 2-cyanomethylbenzoate with stirring under an ice-cooling in a stream of nitrogen, and then to the mixture was added 3.02 g of 2-chlorophenyl isothiocyanate for 10 minutes. The mixture was stirred under an ice-cooling for 10 minutes. To the reaction mixture was added 2.72 g of methyl bromoacetate for 10 minutes, and the mixture was stirred for 80 minutes at room temperature. The reaction mixture was cooled under an ice-bath, and 363 mg of potassium t-butoxide was added to the cold mixture. The mixture was stirred for 1 hour under an ice-cooling. To the reaction mixture was added 70 ml of water for 2 minutes, and the mixture was stirred for 15 minutes. Precipitates were collected by a filtration, and successively washed with water, methanol and hexane, and dried under reduced pressure to obtain 4.87 g of the desired product as white colorless crystals. cooling in a stream of nitrogen The mixture was stirred under an ice- cooling for 10 minutes the mixture was stirred for 80 minutes at room temperature The reaction mixture was cooled under an ice-bath The mixture was stirred for 1 hour under an ice- cooling the mixture was stirred for 15 minutes Precipitates were collected by a filtration successively washed with water, methanol and hexane dried under reduced pressure

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

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (1.6 M, 7.5 ml, 12 mmol) was added dropwise at −78° C. over 5 min to a stirred solution of methyl 2-cyanomethylbenzoate (Tetrahedron Lett., 1991, 32, 4133-4134) (2.10 g, 12 mmol) in dry THF (50 ml) under nitrogen. The deep red solution was stirred at −78° C. for 10 min, followed by the addition of a solution of phenyl azide (1.47 g, 12.3 mmol) in dry THF (10 ml). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min, becoming bright blue. Saturated aqueous ammonium chloride (50 ml) was added and the mixture was acidified to pH 5 with 1M citric acid. The white precipitate was collected and washed with water and diethyl ether, then dried to give 3-phenyl-1,2,3-triazolo[4,5-c]isoquinolin-5-one (2.00 g, 64%). δH (360 MHz; DMSO) 7.58-7.68 (4H, m), 7.80-7.84 (2H, m), 7.93 (1H, ddd, J=8, 8 and 1), 8.30 (2H, d, J=8) and 12.80 (1H, s); m/z (ES+) 263 (M+H+). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min The white precipitate was collected washed with water and diethyl ether dried

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (1.6 M, 7.5 ml, 12 mmol) was added dropwise at −78° C. over 5 min to a stirred solution of methyl 2-cyanomethylbenzoate (Tetrahedron Lett., 1991, 32, 4133-4134) (2.10 g, 12 mmol) in dry THF (50 ml) under nitrogen. The deep red solution was stirred at −78° C. for 10 min, followed by the addition of a solution of phenyl azide (1.47 g, 12.3 mmol) in dry THF (10 ml). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min, becoming bright blue. Saturated aqueous ammonium chloride (50 ml) was added and the mixture was acidified to pH 5 with 1M citric acid. The white precipitate was collected and washed with water and diethyl ether, then dried to give 3-phenyl-1,2,3-triazolo[4,5-c]isoquinolin-5-one (2.00 g, 64%). δH (360 MHz; DMSO) 7.58-7.68 (4H, m), 7.80-7.84 (2H, m), 7.93 (1H, ddd, J=8, 8 and 1), 8.30 (2H, d, J=8) and 12.80 (1H, s); m/z (ES+) 263 (M+H+). The green solution was stirred at −78° C. for 1.5 h then warmed to r.t. over 30 min The white precipitate was collected washed with water and diethyl ether dried

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-cyanomethylbenzoate (10.5 g, 60.0 mmol) in aq. NaOH (66 mL, 66 mmol, 1N solution) was heated at 40° C. for 5 h and it became a clear solution. The mixture was cooled to 0° C. and acidified to pH 1 using 6N aq. HCl. The resulting white solid was collected by filtration. 1H NMR (CD3OD): δ=4.27 (s, 2H), 7.46 (td, J=7.8, 1.0 Hz, 1H), 7.54-7.60 (m, 2H), 8.09 (dd, J=7.8, 1.3 Hz, 1H). The mixture was cooled to 0° C. The resulting white solid was collected by filtration

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of methyl 2-cyanomethylbenzoate (10.5 g, 60.0 mmol) in aq. NaOH (66 mL, 66 mmol, 1N solution) was heated at 40° C. for 5 h and it became a clear solution. The mixture was cooled to 0° C. and acidified to pH 1 using 6N aq. HCl. The resulting white solid was collected by filtration. 1H NMR (CD3OD): δ=4.27 (s, 2H), 7.46 (td, J=7.8, 1.0 Hz, 1H), 7.54-7.60 (m, 2H), 8.09 (dd, J=7.8, 1.3 Hz, 1H). The mixture was cooled to 0° C. The resulting white solid was collected by filtration

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

Procedure: To a solution of 2-cyanomethylbenzoic acid methyl ester (1.75 g, 10 mmol) in THF (15 mL) is added LiBH4 (660 mg, 30 mmol) and the mixture is stirred at RT for 3 h. The mixture is quenched with MeOH then water is added. The mixture is extracted with EtOAc and the organic phase is washed with 1N HCl and brine then is dried over magnesium sulfate. The solvent is removed under reduced pressure to give the title compound which is used directly in the next step. The mixture is quenched with MeOH water is added The mixture is extracted with EtOAc the organic phase is washed with 1N HCl and brine then is dried over magnesium sulfate The solvent is removed under reduced pressure

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

Procedure: To a solution of 2-cyanomethylbenzoic acid methyl ester (1.75 g, 10 mmol) in THF (15 mL) is added LiBH4 (660 mg, 30 mmol) and the mixture is stirred at RT for 3 h. The mixture is quenched with MeOH then water is added. The mixture is extracted with EtOAc and the organic phase is washed with 1N HCl and brine then is dried over magnesium sulfate. The solvent is removed under reduced pressure to give the title compound which is used directly in the next step. The mixture is quenched with MeOH water is added The mixture is extracted with EtOAc the organic phase is washed with 1N HCl and brine then is dried over magnesium sulfate The solvent is removed under reduced pressure

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

Procedure: With gentle heating, 175 g (1.08 mol) of 2-cyanomethyl-benzoic acid (for preparation see: Org. Synthesis, Coll, Vol. 3,174) are dissolved in 1.7 liters of CH2Cl2; 242 ml (=90%, 1.6 mol) of dimethylformamide dimethylacetal are added dropwise at room temperature, and stirring is carried out for 38 hours to complete the reaction. The reaction mixture is washed with 2×1.2 liters of saturated NaHCO3 solution and brine. The aqueous phases are extracted using 2 portions of CH2Cl2, and the organic phases are dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2; ethyl acetate/hexane 1:4, applied in ethyl acetate/hexane/CH2Cl2) yields the title compound: m.p. 49-50° C.; 1H NMR (DMSO-d6) 7.96 (d, 1H), 7.66 (t, 1H), 7.57 (d, 1H), 7.51 (t, 1H), 4.26 (s, 2H), 3.86 (s, 3H); Anal. calc. (C10H9NO2) C 68.56%, H 5.18%, N 8.00%; found C 68.5%, H 5.1%, N 7.9%. the reaction The reaction mixture is washed with 2×1.2 liters of saturated NaHCO3 solution and brine The aqueous phases are extracted the organic phases are dried (Na2SO4) concentrated by evaporation