diethyl 2-[(4-bromophenyl)methyl]propanedioate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of sodium hydroxide (175 g) in water (800 ml) was added to a solution of diethyl (4-bromophenyl)methylmalonate (150 g) in ethanol (850 ml) and the mixture was heated under reflux for 9 hours. Volatile material was removed by evaporation and the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml). The solution was heated under reflux for 2.5 hours, filtered through a bed of diatomaceous earth and the filtrate was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solution was concentrated and the residue was heated at 200° C. until evolution of carbon dioxide ceased. The residue was dissolved in 1M sodium hydroxide solution (500 ml) and the solution was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solvent material was removed by evaporation to give 3-(4-bromophenyl)-2-methylpropionic acid (91 g), m.p. 72°-73° C.; 1H NMR (d6 -DMSO): 1.0 (d, 3 H), 2.05-2.15 (m, 2 H), 2.85-2.9 (m, 1 H), 7.1 (d, 2 H), 7.4 (d, 2 H). the mixture was heated under reflux for 9 hours Volatile material was removed by evaporation the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml) The solution was heated under reflux for 2.5 hours filtered through a bed of diatomaceous earth The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solution was concentrated The residue was dissolved in 1M sodium hydroxide solution (500 ml) The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solvent material was removed by evaporation

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

実験手順: A solution of diethyl methylmalonate (87 g) in absolute ethanol (100 ml) was added to a pre-formed solution of sodium (11.5 g) in ethanol (400 ml) under argon. A hot solution of p-bromobenzylbromide (125 g) in absolute alcohol (200 ml) was added rapidly with vigorous stirring, which was continued for 3 days and the solid so formed was removed by filtration. The filtrate was evaporated and the residue dissolved in ethyl acetate (1 l), washed with brine (250 ml), dried (MgSO4) and evaporated. The residual oil was distilled under vacuum to give diethyl (4-bromophenyl)methylmalonate (150.7 g) b.p. 130-133/0.03 mm Hg; 1H NMR (d6 -DMSO): 1.33 (t, 6 H), 1.4 (s, 3 H), 3.27 (s, 2 H), 4.30 (q, 4 H), 7.23 (d, 2 H), 7.6 (d, 2 H) the solid so formed was removed by filtration The filtrate was evaporated the residue dissolved in ethyl acetate (1 l) washed with brine (250 ml) dried (MgSO4) evaporated The residual oil was distilled under vacuum

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of sodium hydroxide (175 g) in water (800 ml) was added to a solution of diethyl (4-bromophenyl)methylmalonate (150 g) in ethanol (850 ml) and the mixture was heated under reflux for 9 hours. Volatile material was removed by evaporation and the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml). The solution was heated under reflux for 2.5 hours, filtered through a bed of diatomaceous earth and the filtrate was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solution was concentrated and the residue was heated at 200° C. until evolution of carbon dioxide ceased. The residue was dissolved in 1M sodium hydroxide solution (500 ml) and the solution was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solvent material was removed by evaporation to give 3-(4-bromophenyl)-2-methylpropionic acid (91 g), m.p. 72-73° C.; 1H NMR (d6 -DMSO): 1.0 (d, 3H), 2.05-2.15 (m, 2H), 2.85-2.9 (m, 1H), 7.1 (d, 2H), 7.4 (d, 2H). the mixture was heated under reflux for 9 hours Volatile material was removed by evaporation the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml) The solution was heated under reflux for 2.5 hours filtered through a bed of diatomaceous earth The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solution was concentrated The residue was dissolved in 1M sodium hydroxide solution (500 ml) The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solvent material was removed by evaporation

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

実験手順: A solution of diethyl methylmalonate (87 g) in absolute ethanol (100 ml) was added to a pre-formed solution of sodium (11.5 g) in ethanol (400 ml) under argon. A hot solution of p-bromobenzylbromide (125 g) in absolute alcohol (200 ml) was added rapidly with vigorous stirring, which was continued for 3 days and the solid so formed was removed by filtration. The filtrate was evaporated and the residue dissolved in ethyl acetate (11), washed with brine (250 ml), dried (MgSO4) and evaporated. The residual oil was distilled under vacuum to give diethyl (4-bromophenyl)methylmalonate (150.7 g) b.p. 130-133/0.03 mm Hg; 1H NMR (d6 -DMSO): 1.33 (t, 6H), 1.4 (s, 3H), 3.27 (s, 2H), 4.30 (q, 4H), 7.23 (d, 2H), 7.6 (d, 2H), the solid so formed was removed by filtration The filtrate was evaporated the residue dissolved in ethyl acetate (11) washed with brine (250 ml) dried (MgSO4) evaporated The residual oil was distilled under vacuum

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

実験手順: A solution of diethyl methylmalonate (87 g) in absolute ethanol (100 ml) was added to a pre-formed solution of sodium (11.5 g) in ethanol (400 ml) under argon. A hot solution of p-bromobenzylbromide (125 g) in absolute alcohol (200 ml) was added rapidly with vigorous stirring, which was continued for 3 days and the solid so formed was removed by filtration. The filtrate was evaporated and the residue dissolved in ethyl acetate (11), washed with brine (250 ml), dried (MgSO4) and evaporated. The residual oil was distilled under vacuum to give diethyl (4-bromophenyl)methylmalonate (150.7 g) b.p. 130-133/0.03 mm Hg; 1H NMR (d6 -DMSO): 1.33 (t, 6H), 1.4 (s, 3H), 3.27 (s, 2H), 4.30 (q, 4H), 7.23 (d, 2H), 7.6 (d, 2H), the solid so formed was removed by filtration The filtrate was evaporated the residue dissolved in ethyl acetate (11) washed with brine (250 ml) dried (MgSO4) evaporated The residual oil was distilled under vacuum

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

実験手順: Diethyl 2-(4-bromobenzyl)malonate (40 g, 13 mmol) and KOH (42.8 g, 76 mmol) was dissolved in a mixture of HOAc-H2O-THF (1:2:3, 200 mL), the mixture was refluxed for 12 hours. The solvent was removed in vacuo, the residue was added HCl aqueous, then extracted with EtOAc, washed with brine, dried over Na2SO4, concentrated to give 2-(4-bromobenzyl)malonic acid (31 g, 95%). the mixture was refluxed for 12 hours The solvent was removed in vacuo the residue was added HCl aqueous extracted with EtOAc washed with brine dried over Na2SO4 concentrated

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

実験手順: Diethyl 2-(4-bromobenzyl)malonate (40 g, 13 mmol) and KOH (42.8 g, 76 mmol) was dissolved in a mixture of HOAc-H2O-THF (1:2:3, 200 mL), the mixture was refluxed for 12 hours. The solvent was removed in vacuo, the residue was added HCl aqueous, then extracted with EtOAc, washed with brine, dried over Na2SO4, concentrated to give 2-(4-bromobenzyl)malonic acid (31 g, 95%). the mixture was refluxed for 12 hours The solvent was removed in vacuo the residue was added HCl aqueous extracted with EtOAc washed with brine dried over Na2SO4 concentrated

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of sodium hydroxide (175 g) in water (800 ml) was added to a solution of diethyl (4-bromophenyl)methylmalonate (150 g) in ethanol (850 ml) and the mixture was heated under reflux for 9 hours. Volatile material was removed by evaporation and the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml). The solution was heated under reflux for 2.5 hours, filtered through a bed of diatomaceous earth and the filtrate was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solution was concentrated and the residue was heated at 200° C. until evolution of carbon dioxide ceased. The residue was dissolved in 1M sodium hydroxide solution (500 ml) and the solution was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solvent material was removed by evaporation to give 3-(4-bromophenyl)-2-methylpropionic acid (91 g), m.p. 72°-73° C.; 1H NMR (d6 -DMSO): 1.0 (d, 3 H), 2.05-2.15 (m, 2 H), 2.85-2.9 (m, 1 H), 7.1 (d, 2 H), 7.4 (d, 2 H). the mixture was heated under reflux for 9 hours Volatile material was removed by evaporation the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml) The solution was heated under reflux for 2.5 hours filtered through a bed of diatomaceous earth The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solution was concentrated The residue was dissolved in 1M sodium hydroxide solution (500 ml) The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solvent material was removed by evaporation

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

実験手順: A solution of diethyl methylmalonate (87 g) in absolute ethanol (100 ml) was added to a pre-formed solution of sodium (11.5 g) in ethanol (400 ml) under argon. A hot solution of p-bromobenzylbromide (125 g) in absolute alcohol (200 ml) was added rapidly with vigorous stirring, which was continued for 3 days and the solid so formed was removed by filtration. The filtrate was evaporated and the residue dissolved in ethyl acetate (1 l), washed with brine (250 ml), dried (MgSO4) and evaporated. The residual oil was distilled under vacuum to give diethyl (4-bromophenyl)methylmalonate (150.7 g) b.p. 130-133/0.03 mm Hg; 1H NMR (d6 -DMSO): 1.33 (t, 6 H), 1.4 (s, 3 H), 3.27 (s, 2 H), 4.30 (q, 4 H), 7.23 (d, 2 H), 7.6 (d, 2 H) the solid so formed was removed by filtration The filtrate was evaporated the residue dissolved in ethyl acetate (1 l) washed with brine (250 ml) dried (MgSO4) evaporated The residual oil was distilled under vacuum

反応条件: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of sodium hydroxide (175 g) in water (800 ml) was added to a solution of diethyl (4-bromophenyl)methylmalonate (150 g) in ethanol (850 ml) and the mixture was heated under reflux for 9 hours. Volatile material was removed by evaporation and the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml). The solution was heated under reflux for 2.5 hours, filtered through a bed of diatomaceous earth and the filtrate was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solution was concentrated and the residue was heated at 200° C. until evolution of carbon dioxide ceased. The residue was dissolved in 1M sodium hydroxide solution (500 ml) and the solution was acidified with 6M sulphuric acid. The mixture was extracted with ether (4×500 ml) and the extracts were dried (MgSO4). The solvent material was removed by evaporation to give 3-(4-bromophenyl)-2-methylpropionic acid (91 g), m.p. 72°-73° C.; 1H NMR (d6 -DMSO): 1.0 (d, 3 H), 2.05-2.15 (m, 2 H), 2.85-2.9 (m, 1 H), 7.1 (d, 2 H), 7.4 (d, 2 H). the mixture was heated under reflux for 9 hours Volatile material was removed by evaporation the residue was dissolved in a solution of sodium hydroxide (130 g) in water (250 ml) The solution was heated under reflux for 2.5 hours filtered through a bed of diatomaceous earth The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solution was concentrated The residue was dissolved in 1M sodium hydroxide solution (500 ml) The mixture was extracted with ether (4×500 ml) the extracts were dried (MgSO4) The solvent material was removed by evaporation

反応条件: temp:0.00; pressure:0.00; stir: