dimethyl 3-(bromomethyl)benzene-1,2-dicarboxylate

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

実験手順: A solution of methyl-carbamic acid t-butyl ester (5.0 g, 38.0 mmol) in DMF (50 mL) was chilled in an ice bath, and NaH (60%, 1.7 g, 41.8 mmol) was added in portions at 10C. The mixture was stirred for an additional 30 minutes. A solution of 3-bromomethyl-phthalic acid dimethyl ester (10.9 g, 38.0 mmol) in DMF (20 mL) was slowly added, keeping the temperature at 10-15° C. The resulting mixture was stirred at room temperature overnight. The mixture was poured into ice water (400 mL) and extracted with EtOAc (4×70 mL). The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). The solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-[(t-butoxycarbonyl-methyl-amino)-methyl]-phthalic dimethyl ester (7.7 g, 60%) as an oil: 1H NMR (CDCl3) δ 7.93-7.89 (m, 1H), 7.49-7.46 (m, 2H), 4.46 (s, 2H), 3.94 (s, 3H), 3.89 (s, 3H), 2.87-2.76 (b, 3H), 1.49-1.42 (b, 9H). at 10-15° C The resulting mixture was stirred at room temperature overnight extracted with EtOAc (4×70 mL) The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) The solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)

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

実験手順: A solution of methyl-carbamic acid t-butyl ester (5.0 g, 38.0 mmol) in DMF (50 mL) was chilled in an ice bath, and NaH (60%, 1.7 g, 41.8 mmol) was added in portions at 10C. The mixture was stirred for an additional 30 minutes. A solution of 3-bromomethyl-phthalic acid dimethyl ester (10.9 g, 38.0 mmol) in DMF (20 mL) was slowly added, keeping the temperature at 10-15° C. The resulting mixture was stirred at room temperature overnight. The mixture was poured into ice water (400 mL) and extracted with EtOAc (4×70 mL). The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). The solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-[(t-butoxycarbonyl-methyl-amino)-methyl]-phthalic dimethyl ester (7.7 g, 60%) as an oil: 1H NMR (CDCl3) δ 7.93-7.89 (m, 1H), 7.49-7.46 (m, 2H), 4.46 (s, 2H), 3.94 (s, 3H), 3.89 (s, 3H), 2.87-2.76 (b, 3H), 1.49-1.42 (b, 9H). at 10-15° C The resulting mixture was stirred at room temperature overnight extracted with EtOAc (4×70 mL) The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) The solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 3-methyl-phthalic dimethyl ester (12.1 g, 57.9 mmol) and N-bromosuccinimide (12.4 g, 69.5 mmol) in acetonitrile (150 mL) was heated at 70° C. (oil bath), while a 200 W light bulb situated 2 cm away was shining on the reaction mixture overnight. The resulting mixture was cooled and concentrated. The residue was dissolved in ethyl acetate (150 mL), washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). Solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-bromomethyl-phthalic dimethyl ester (13.9 g, 83%) as a solid: 1H NMR (CDCl3) δ 7.94-7.90 (dd, J=1.1 and 7.9 Hz, 1H), 7.65-7.62 (dd, J=1.0 and 6.9 Hz, 1H), 7.47 (t, J=7.8H, 1H), 4.54 (s, 2H), 3.97 (s, 3H), 3.90 (s, 3H). away was shining on the reaction mixture overnight The resulting mixture was cooled concentrated The residue was dissolved in ethyl acetate (150 mL) washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) Solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 3-methyl-phthalic dimethyl ester (12.1 g, 57.9 mmol) and N-bromosuccinimide (12.4 g, 69.5 mmol) in acetonitrile (150 mL) was heated at 70° C. (oil bath), while a 200 W light bulb situated 2 cm away was shining on the reaction mixture overnight. The resulting mixture was cooled and concentrated. The residue was dissolved in ethyl acetate (150 mL), washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). Solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-bromomethyl-phthalic dimethyl ester (13.9 g, 83%) as a solid: 1H NMR (CDCl3) δ 7.94-7.90 (dd, J=1.1 and 7.9 Hz, 1H), 7.65-7.62 (dd, J=1.0 and 6.9 Hz, 1H), 7.47 (t, J=7.8H, 1H), 4.54 (s, 2H), 3.97 (s, 3H), 3.90 (s, 3H). away was shining on the reaction mixture overnight The resulting mixture was cooled concentrated The residue was dissolved in ethyl acetate (150 mL) washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) Solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)

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

実験手順: A solution of methyl-carbamic acid t-butyl ester (5.0 g, 38.0 mmol) in DMF (50 mL) was chilled in an ice bath, and NaH (60%, 1.7 g, 41.8 mmol) was added in portions at 10C. The mixture was stirred for an additional 30 minutes. A solution of 3-bromomethyl-phthalic acid dimethyl ester (10.9 g, 38.0 mmol) in DMF (20 mL) was slowly added, keeping the temperature at 10-15° C. The resulting mixture was stirred at room temperature overnight. The mixture was poured into ice water (400 mL) and extracted with EtOAc (4×70 mL). The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). The solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-[(t-butoxycarbonyl-methyl-amino)-methyl]-phthalic dimethyl ester (7.7 g, 60%) as an oil: 1H NMR (CDCl3) δ 7.93-7.89 (m, 1H), 7.49-7.46 (m, 2H), 4.46 (s, 2H), 3.94 (s, 3H), 3.89 (s, 3H), 2.87-2.76 (b, 3H), 1.49-1.42 (b, 9H). at 10-15° C The resulting mixture was stirred at room temperature overnight extracted with EtOAc (4×70 mL) The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) The solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 3-methyl-phthalic dimethyl ester (12.1 g, 57.9 mmol) and N-bromosuccinimide (12.4 g, 69.5 mmol) in acetonitrile (150 mL) was heated at 70° C. (oil bath), while a 200 W light bulb situated 2 cm away was shining on the reaction mixture overnight. The resulting mixture was cooled and concentrated. The residue was dissolved in ethyl acetate (150 mL), washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). Solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-bromomethyl-phthalic dimethyl ester (13.9 g, 83%) as a solid: 1H NMR (CDCl3) δ 7.94-7.90 (dd, J=1.1 and 7.9 Hz, 1H), 7.65-7.62 (dd, J=1.0 and 6.9 Hz, 1H), 7.47 (t, J=7.8H, 1H), 4.54 (s, 2H), 3.97 (s, 3H), 3.90 (s, 3H). away was shining on the reaction mixture overnight The resulting mixture was cooled concentrated The residue was dissolved in ethyl acetate (150 mL) washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) Solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)

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

実験手順: A solution of methyl-carbamic acid t-butyl ester (5.0 g, 38.0 mmol) in DMF (50 mL) was chilled in an ice bath, and NaH (60%, 1.7 g, 41.8 mmol) was added in portions at 10C. The mixture was stirred for an additional 30 minutes. A solution of 3-bromomethyl-phthalic acid dimethyl ester (10.9 g, 38.0 mmol) in DMF (20 mL) was slowly added, keeping the temperature at 10-15° C. The resulting mixture was stirred at room temperature overnight. The mixture was poured into ice water (400 mL) and extracted with EtOAc (4×70 mL). The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). The solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-[(t-butoxycarbonyl-methyl-amino)-methyl]-phthalic dimethyl ester (7.7 g, 60%) as an oil: 1H NMR (CDCl3) δ 7.93-7.89 (m, 1H), 7.49-7.46 (m, 2H), 4.46 (s, 2H), 3.94 (s, 3H), 3.89 (s, 3H), 2.87-2.76 (b, 3H), 1.49-1.42 (b, 9H). at 10-15° C The resulting mixture was stirred at room temperature overnight extracted with EtOAc (4×70 mL) The combined EtOAc extracts were washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) The solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A stirred mixture of 3-methyl-phthalic dimethyl ester (12.1 g, 57.9 mmol) and N-bromosuccinimide (12.4 g, 69.5 mmol) in acetonitrile (150 mL) was heated at 70° C. (oil bath), while a 200 W light bulb situated 2 cm away was shining on the reaction mixture overnight. The resulting mixture was cooled and concentrated. The residue was dissolved in ethyl acetate (150 mL), washed with water (3×50 mL) and brine (50 mL), and dried (MgSO4). Solvent was removed in vacuo, and the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2) to give 3-bromomethyl-phthalic dimethyl ester (13.9 g, 83%) as a solid: 1H NMR (CDCl3) δ 7.94-7.90 (dd, J=1.1 and 7.9 Hz, 1H), 7.65-7.62 (dd, J=1.0 and 6.9 Hz, 1H), 7.47 (t, J=7.8H, 1H), 4.54 (s, 2H), 3.97 (s, 3H), 3.90 (s, 3H). away was shining on the reaction mixture overnight The resulting mixture was cooled concentrated The residue was dissolved in ethyl acetate (150 mL) washed with water (3×50 mL) and brine (50 mL) dried (MgSO4) Solvent was removed in vacuo the residue was purified by flash chromatography (SiO2, Hexane:EtOAc 8:2)