2-[2-(hydroxymethyl)phenyl]acetonitrile

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

Procedure: To a suspension of sodium borohydride (454 mg, 12.0 mmol) in THF (20 mL) was slowly added a solution of 2-cyanomethylbenzoic acid (1.61 g, 10.0 mmol) in THF (20 mL), then a solution of iodine (1.30 g, 5.0 mmol) in THF (20 mL) was slowly added at rt. The resulting mixture was stirred at rt for 1 h. The reaction was quenched with 3 N HCl (10 mL), then extracted with Et2O (3×20 mL). The combined organic phases were washed with brine (20 mL), and dried over anhydrous sodium sulfate. The residue was purified by silica gel chromatography (Hex:EtOAc=80:20→60:40) to give the title compound as a yellow oil. 1H NMR (CD3OD): δ=3.98 (s, 2H), 4.27 (s, 2H), 7.33 (m, 2H), 7.41 (m, 2H). The reaction was quenched with 3 N HCl (10 mL) extracted with Et2O (3×20 mL) The combined organic phases were washed with brine (20 mL) dried over anhydrous sodium sulfate The residue was purified by silica gel chromatography (Hex:EtOAc=80:20→60:40)

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

Procedure: After the completion of reaction, the concentration of 3-isochromanone was analyzed by GC analysis and then the yield of 3-isochromanone was calculated. As a result, the yield was found to be 75% based on α-chloro-α′-cyano-o-xylene. At this time, the conversion ratio of α-chloro-α′-cyano-o-xylene was 100% and the by-product α-hydroxy-α′-cyano-o-xylene was produced in a yield of 2.2%. Furthermore, as a result of the HPLC analysis, α-carboxy-α′-hydroxy-o-xylene and α-aminocarboxy-α′-hydroxy-o-xylene were found to be present as by-products in a concentration of 18% based on α-chloro-α′-cyano-o-xylene. After the completion of reaction

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

Procedure: After completion of the reaction, the concentration of 3-isochromanone was analyzed by GC analysis and then the yield of 3-isochromanone was calculated. As a result, the yield was found to be 95% based on α-chloro-α′-cyano-o-xylene. At this time, the conversion ratio of α-chloro-α′-cyano-o-xylene was 100% and the by-product compound (α-hydroxy-α′-cyano-o-xylene) where the halogen moiety was hydrolyzed was produced in a yield of 1.6%. After completion of the reaction

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: After the completion of reaction, the concentration of 3-isochromanone was analyzed by GC analysis and then the yield of 3-isochromanone was calculated. As a result, the yield was found to be 75% based on α-chloro-α′-cyano-o-xylene. At this time, the conversion ratio of α-chloro-α′-cyano-o-xylene was 100% and the by-product α-hydroxy-α′-cyano-o-xylene was produced in a yield of 2.2%. Furthermore, as a result of the HPLC analysis, α-carboxy-α′-hydroxy-o-xylene and α-aminocarboxy-α′-hydroxy-o-xylene were found to be present as by-products in a concentration of 18% based on α-chloro-α′-cyano-o-xylene. After the completion of reaction

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

Procedure: After completion of the reaction, the concentration of 3-isochromanone was analyzed by GC analysis and then the yield of 3-isochromanone was calculated. As a result, the yield was found to be 95% based on α-chloro-α′-cyano-o-xylene. At this time, the conversion ratio of α-chloro-α′-cyano-o-xylene was 100% and the by-product compound (α-hydroxy-α′-cyano-o-xylene) where the halogen moiety was hydrolyzed was produced in a yield of 1.6%. After completion of the reaction

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

Procedure: To a suspension of sodium borohydride (454 mg, 12.0 mmol) in THF (20 mL) was slowly added a solution of 2-cyanomethylbenzoic acid (1.61 g, 10.0 mmol) in THF (20 mL), then a solution of iodine (1.30 g, 5.0 mmol) in THF (20 mL) was slowly added at rt. The resulting mixture was stirred at rt for 1 h. The reaction was quenched with 3 N HCl (10 mL), then extracted with Et2O (3×20 mL). The combined organic phases were washed with brine (20 mL), and dried over anhydrous sodium sulfate. The residue was purified by silica gel chromatography (Hex:EtOAc=80:20→60:40) to give the title compound as a yellow oil. 1H NMR (CD3OD): δ=3.98 (s, 2H), 4.27 (s, 2H), 7.33 (m, 2H), 7.41 (m, 2H). The reaction was quenched with 3 N HCl (10 mL) extracted with Et2O (3×20 mL) The combined organic phases were washed with brine (20 mL) dried over anhydrous sodium sulfate The residue was purified by silica gel chromatography (Hex:EtOAc=80:20→60:40)

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