methyl 2-(3-oxo-1,2-dihydroisoindol-1-yl)acetate

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

Procedure: A solution of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid (described by F. M. Rowe et al., supra, 130 g, 0.682 mol) in methanol (1300 ml) containing 6.5 g of p-toluenesulfonic acid is refluxed with stirring for 3.5 hr. Most of the methanol is evaporated and the residue is dissolved in chloroform. The solution is washed with 5% aqueous sodium bicarbonate and water, dried and evaporated. The residue (125 g) is crystallized from isopropanol to give methyl 2,3-dihydro-3-oxo-1H-isoindole-1-acetate, mp 136°-138° C. is refluxed Most of the methanol is evaporated the residue is dissolved in chloroform The solution is washed with 5% aqueous sodium bicarbonate and water dried evaporated The residue (125 g) is crystallized from isopropanol

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

Procedure: To a solution of (3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetic acid (2.0 g, 10.4 mmol) in 100 mL methanol was added 2 mL conc. H2SO4 over 5 min. The mixture was stirred at room temperature for 16 h. Solvent was evaporated, the crude oil was dissolved in 200 mL EtOAc, then washed with 50 mL sat'd NaHCO3 and 2×50 mL water. The organic phase was dried (Na2SO4), filtered, and solvent was evaporated. The title compound was isolated as a yellow oil (2.1 g, 98%). Solvent was evaporated the crude oil was dissolved in 200 mL EtOAc washed with 50 mL The organic phase was dried (Na2SO4) filtered solvent was evaporated

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

Procedure: To a solution of (3-oxo-2,3-dihydro-1H-isoindol-1-yl)-acetic acid (2.0 g, 10.4 mmol) in 100 mL methanol was added 2 mL conc. H2SO4 over 5 min. The mixture was stirred at room temperature for 16 h. Solvent was evaporated, the crude oil was dissolved in 200 mL EtOAc, then washed with 50 mL sat'd NaHCO3 and 2×50 mL water. The organic phase was dried (Na2SO4), filtered, and solvent was evaporated. The title compound was isolated as a yellow oil (2.1 g, 98%). Solvent was evaporated the crude oil was dissolved in 200 mL EtOAc washed with 50 mL The organic phase was dried (Na2SO4) filtered solvent was evaporated

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

Procedure: 2,3-Dihydro-3-oxo-1H-isoindole-1-acetic acid methyl ester (1.5 g, 7.5 mmol) is added to a solution of NaBH4 (1.4 g, 37.6 mmol) in 50 mL of methanol at room temperature, and the mixture is stirred overnight. The reaction is quenched by addition of gaseous HCl until the pH=1. The methanol is evaporated, and the remaining solid is stirred in 100 mL of CH2Cl2 for 15 minutes. The solid is removed by filtration through Celite® 545. Evaporation of the filtrate gives 1.3 g (90% yield) of 1,3-dihydro-3-(2-hydroxyethyl)-2H-isoindol-1-one as an oil. The reaction is quenched by addition of gaseous HCl until the pH=1 The methanol is evaporated the remaining solid is stirred in 100 mL of CH2Cl2 for 15 minutes The solid is removed by filtration through Celite® 545 Evaporation of the filtrate

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

Procedure: A solution of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid (Rowe F. M., et al., J. Chem. Soc., 1098, 1936) (20 g, 104.6 mmol) in 100 mL of DMF is added to a suspension of NaH (2.5 g, 104.6 mmol) in 200 mL of DMF at room temperature under argon. Some cooling is required during the addition to keep the mixture at room temperature. The mixture is stirred at room temperature for 30 minutes. Methyl iodide (14.8 g, 104.6 mmol) is added, and the mixture is stirred at room temperature overnight. The reaction is quenched by addition of 5 mL of acetic acid, and the DMF is evaporated. Residual DMF is removed by heating the wet solid in a steam bath under high vacuum. The dried solid is stirred into 300 mL of CH2Cl2 for 1 hour. The solid is removed by filtration, and the filtrate is evaporated to give 12 g (56% yield) of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid methyl ester. Some cooling is required during the addition at room temperature the mixture is stirred at room temperature overnight The reaction is quenched by addition of 5 mL of acetic acid the DMF is evaporated Residual DMF is removed by heating the wet solid in a steam bath under high vacuum The dried solid is stirred into 300 mL of CH2Cl2 for 1 hour The solid is removed by filtration the filtrate is evaporated

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

Procedure: A solution of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid (Rowe F. M., et al., J. Chem. Soc., 1098, 1936) (20 g, 104.6 mmol) in 100 mL of DMF is added to a suspension of NaH (2.5 g, 104.6 mmol) in 200 mL of DMF at room temperature under argon. Some cooling is required during the addition to keep the mixture at room temperature. The mixture is stirred at room temperature for 30 minutes. Methyl iodide (14.8 g, 104.6 mmol) is added, and the mixture is stirred at room temperature overnight. The reaction is quenched by addition of 5 mL of acetic acid, and the DMF is evaporated. Residual DMF is removed by heating the wet solid in a steam bath under high vacuum. The dried solid is stirred into 300 mL of CH2Cl2 for 1 hour. The solid is removed by filtration, and the filtrate is evaporated to give 12 g (56% yield) of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid methyl ester. Some cooling is required during the addition at room temperature the mixture is stirred at room temperature overnight The reaction is quenched by addition of 5 mL of acetic acid the DMF is evaporated Residual DMF is removed by heating the wet solid in a steam bath under high vacuum The dried solid is stirred into 300 mL of CH2Cl2 for 1 hour The solid is removed by filtration the filtrate is evaporated

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

Procedure: A solution of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid (Rowe F. M., et al., J. Chem. Soc., 1098, 1936) (20 g, 104.6 mmol) in 100 mL of DMF is added to a suspension of NaH (2.5 g, 104.6 mmol) in 200 mL of DMF at room temperature under argon. Some cooling is required during the addition to keep the mixture at room temperature. The mixture is stirred at room temperature for 30 minutes. Methyl iodide (14.8 g, 104.6 mmol) is added, and the mixture is stirred at room temperature overnight. The reaction is quenched by addition of 5 mL of acetic acid, and the DMF is evaporated. Residual DMF is removed by heating the wet solid in a steam bath under high vacuum. The dried solid is stirred into 300 mL of CH2Cl2 for 1 hour. The solid is removed by filtration, and the filtrate is evaporated to give 12 g (56% yield) of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid methyl ester. Some cooling is required during the addition at room temperature the mixture is stirred at room temperature overnight The reaction is quenched by addition of 5 mL of acetic acid the DMF is evaporated Residual DMF is removed by heating the wet solid in a steam bath under high vacuum The dried solid is stirred into 300 mL of CH2Cl2 for 1 hour The solid is removed by filtration the filtrate is evaporated

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

Procedure: A solution of 1,3-dihydro-3-oxo-2H-isoindole-1-acetic acid (described by F. M. Rowe et al., J. Chem. Soc., 1098 (1936) 130 g, 0.682 mol) in methanol (1300 ml) containing 6.5 g of p-toluenesulfonic acid was refluxed with stirring for 3.5 hr. Most of the methanol was evaporated and the residue was dissolved in chloroform. The solution was washed with 5% aqueous sodium bicarbonate and water, dried and evaporated. The residue (125 g) was crystallized from isopropanol to give methyl 1,3-dihydro-3-oxo-2H-isoindole-1-acetate, mp 136°-138° C. was refluxed Most of the methanol was evaporated the residue was dissolved in chloroform The solution was washed with 5% aqueous sodium bicarbonate and water dried evaporated The residue (125 g) was crystallized from isopropanol

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

Procedure: A solution of 1,3-dihydro-3-oxo-2H-isoindole-1-acetic acid (described by F. M. Rowe et al., J. Chem. Soc., 1098 (1936) 130 g, 0.682 mol) in methanol (1300 ml) containing 6.5 g of p-toluenesulfonic acid was refluxed with stirring for 3.5 hr. Most of the methanol was evaporated and the residue was dissolved in chloroform. The solution was washed with 5% aqueous sodium bicarbonate and water, dried and evaporated. The residue (125 g) was crystallized from isopropanol to give methyl 1,3-dihydro-3-oxo-2H-isoindole-1-acetate, mp 136°-138° C. was refluxed Most of the methanol was evaporated the residue was dissolved in chloroform The solution was washed with 5% aqueous sodium bicarbonate and water dried evaporated The residue (125 g) was crystallized from isopropanol

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

Procedure: A solution of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid (described by F. M. Rowe et al., supra, 130 g, 0.682 mol) in methanol (1300 ml) containing 6.5 g of p-toluenesulfonic acid is refluxed with stirring for 3.5 hr. Most of the methanol is evaporated and the residue is dissolved in chloroform. The solution is washed with 5% aqueous sodium bicarbonate and water, dried and evaporated. The residue (125 g) is crystallized from isopropanol to give methyl 2,3-dihydro-3-oxo-1H-isoindole-1-acetate, mp 136°-138° C. is refluxed Most of the methanol is evaporated the residue is dissolved in chloroform The solution is washed with 5% aqueous sodium bicarbonate and water dried evaporated The residue (125 g) is crystallized from isopropanol

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

Procedure: A solution of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid (described by F. M. Rowe et al., supra, 130 g, 0.682 mol) in methanol (1300 ml) containing 6.5 g of p-toluenesulfonic acid is refluxed with stirring for 3.5 hr. Most of the methanol is evaporated and the residue is dissolved in chloroform. The solution is washed with 5% aqueous sodium bicarbonate and water, dried and evaporated. The residue (125 g) is crystallized from isopropanol to give methyl 2,3-dihydro-3-oxo-1H-isoindole-1-acetate, mp 136°-138° C. is refluxed Most of the methanol is evaporated the residue is dissolved in chloroform The solution is washed with 5% aqueous sodium bicarbonate and water dried evaporated The residue (125 g) is crystallized from isopropanol

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

Procedure: A solution of 2,3-dihydro-3-oxo-1H-isoindole-1-acetic acid (described by F. M. Rowe et al., cited above, 130 g, 0.682 mol) in methanol (1300 ml) containing 6.5 g of p-toluenesulfonic acid is refluxed with stirring for 3.5 hr. Most of the methanol is evaporated and the residue is dissolved in chloroform. The solution is washed with 5% aqueous sodium bicarbonate and water, dried and evaporated. The residue (125 g) is crystallized from isopropanol to give methyl 1,3-dihydro-3-oxo-2H-isoindole-1-acetate, mp 136°-138° C. is refluxed Most of the methanol is evaporated the residue is dissolved in chloroform The solution is washed with 5% aqueous sodium bicarbonate and water dried evaporated The residue (125 g) is crystallized from isopropanol