4-chloro-2-[(5-chloro-2-hydroxyphenyl)methyl]phenol

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol).The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2′-Methylene-bis(4-chloro-phenol) (12 g, 44.6 mmol) is dissolved in DMF (100 mL). Lithium carbonate (3.3 g, 44.6 mmol) is added, followed by benzyl-2-bromoacetate (7.7 mL, 49 mmol). The suspension is stirred at 80° C. for 8 hours. Further benzyl-2-bromoacetate (1 mL, 6.4 mmol) is added and stirring continued at 100° C. for 4 hours. The reaction mixture is evaporated to dryness, water is added to the residue which is acidified to pH 1 with 2 M aqueous HCl and extracted with EtOAc. The organic layer is washed with brine, dried (MgSO4) and evaporated. The crude product is purified by flash column chromatography over silica gel eluting with 4:1 iso-hexane:EtOAc. The product is suspended in iso-hexane, dissolved in the minimum volume of EtOAc, seeded and left to stand. The resultant solid is collected by filtration, washed with iso-hexane and dried to give [4-chloro-2-(5-chloro-2-hydroxy-benzyl)-phenoxy]-acetic acid benzyl ester; m.p.=135-137° C. stirring continued at 100° C. for 4 hours The reaction mixture is evaporated to dryness, water is added to the residue which extracted with EtOAc The organic layer is washed with brine dried (MgSO4) evaporated The crude product is purified by flash column chromatography over silica gel eluting with 4:1 iso-hexane dissolved in the minimum volume of EtOAc left The resultant solid is collected by filtration washed with iso-hexane dried

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2′-Methylene-bis(4-chloro-phenol) (12 g, 44.6 mmol) is dissolved in DMF (100 mL). Lithium carbonate (3.3 g, 44.6 mmol) is added, followed by benzyl-2-bromoacetate (7.7 mL, 49 mmol). The suspension is stirred at 80° C. for 8 hours. Further benzyl-2-bromoacetate (1 mL, 6.4 mmol) is added and stirring continued at 100° C. for 4 hours. The reaction mixture is evaporated to dryness, water is added to the residue which is acidified to pH 1 with 2 M aqueous HCl and extracted with EtOAc. The organic layer is washed with brine, dried (MgSO4) and evaporated. The crude product is purified by flash column chromatography over silica gel eluting with 4:1 iso-hexane:EtOAc. The product is suspended in iso-hexane, dissolved in the minimum volume of EtOAc, seeded and left to stand. The resultant solid is collected by filtration, washed with iso-hexane and dried to give [4-chloro-2-(5-chloro-2-hydroxy-benzyl)-phenoxy]-acetic acid benzyl ester; m.p.=135-137° C. stirring continued at 100° C. for 4 hours The reaction mixture is evaporated to dryness, water is added to the residue which extracted with EtOAc The organic layer is washed with brine dried (MgSO4) evaporated The crude product is purified by flash column chromatography over silica gel eluting with 4:1 iso-hexane dissolved in the minimum volume of EtOAc left The resultant solid is collected by filtration washed with iso-hexane dried

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2′-Methylene-bis(4-chloro-phenol) (12 g, 44.6 mmol) is dissolved in DMF (100 mL). Lithium carbonate (3.3 g, 44.6 mmol) is added, followed by benzyl-2-bromoacetate (7.7 mL, 49 mmol). The suspension is stirred at 80° C. for 8 hours. Further benzyl-2-bromoacetate (1 mL, 6.4 mmol) is added and stirring continued at 100° C. for 4 hours. The reaction mixture is evaporated to dryness, water is added to the residue which is acidified to pH 1 with 2 M aqueous HCl and extracted with EtOAc. The organic layer is washed with brine, dried (MgSO4) and evaporated. The crude product is purified by flash column chromatography over silica gel eluting with 4:1 iso-hexane:EtOAc. The product is suspended in iso-hexane, dissolved in the minimum volume of EtOAc, seeded and left to stand. The resultant solid is collected by filtration, washed with iso-hexane and dried to give [4-chloro-2-(5-chloro-2-hydroxy-benzyl)-phenoxy]-acetic acid benzyl ester; m.p.=135-137° C. stirring continued at 100° C. for 4 hours The reaction mixture is evaporated to dryness, water is added to the residue which extracted with EtOAc The organic layer is washed with brine dried (MgSO4) evaporated The crude product is purified by flash column chromatography over silica gel eluting with 4:1 iso-hexane dissolved in the minimum volume of EtOAc left The resultant solid is collected by filtration washed with iso-hexane dried

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)

反応条件: temp:105.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of bis-(5-chloro-2-hydroxyphenyl)-methane (24.4 g, 90.7 mmol) in dry DMF (340 mL) was added diiodomethane (25.5 g, 95.0 mmol) and potassium carbonate (18.2 g, 132 mmol). The mixture was stirred at 105° C. for 16 h. The mixture was added to ice water (1200 mL) and stirred for 30 min. The product was isolated by filtration, and washed with water and suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL). The mixture was heated at 80° C. for 1 h. The mixture was added to water (600 mL) and 21.45 g (84%) 2,10-dichloro-12H-dibenzo[d,g][1,3]-dioxocin was isolated by filtration. stirred for 30 min The product was isolated by filtration washed with water suspended in a mixture of ethanol (200 mL) and 4N NaOH (50 mL) The mixture was heated at 80° C. for 1 h The mixture was added to water (600 mL)