1,3-二溴-5-(甲氧基甲氧基)苯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium hydride (693 mg, 17.33 mmol, 60%, oil was washed with pentane) in THF (15 mL) was added 3, 5-dibromophenol (3.0 g, 11.55 mmol) at 0° C. and the suspension was stirred for 30 minutes. Then, methoxymethyl chloride (1.4 g, 17.33 mmol) was added at 0° C. The resulting suspension was allowed to warm to room temperature and stirred for 2 days at which time TLC analysis of the mixture indicated the absence of starting material. Then, the reaction mixture was poured into an ice-water (50 mL) and the organic compound was extracted into ethyl acetate (2×100 mL). The combined extracts were washed with brine solution (250 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and the concentration of the solution under reduced pressure gave the crude residue which was purified by using an ISCO 120 g column chromatography, eluting with 5-20% ethyl acetate in hexanes to obtain 1,3-dibromo-5-methoxymethoxy-benzene (2.94 g, 86%) as a white solid: EI(+)-HRMS m/e calcd for C8H8Br2O2 (M)+ 293.8891, found 293.8893. stirred for 2 days at which time TLC analysis of the mixture the organic compound was extracted into ethyl acetate (2×100 mL) The combined extracts were washed with brine solution (250 mL) dried over anhydrous magnesium sulfate Filtration of the drying agent the concentration of the solution under reduced pressure gave the crude residue which was purified eluting with 5-20% ethyl acetate in hexanes

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: n-BuLi (8.34 mL of a 1.6 M solution in Et2O, 13.34 mmol) was added dropwise to a solution cooled to −78° C. of 1,3-dibromo-5-methoxymethoxy-benzene (3.59 g, 12.13 mmol) in anhydrous Et2O (40 mL) under a nitrogen atmosphere. The solution was aged at −78° C. for 45 m, anhydrous DMF (1.03 mL, 13.34 mmol) was added, and the reaction mixture was slowly warmed to RT. The mixture was poured into H2O (50 mL), and the aqueous phase was extracted with Et2O (2×75 mL). The combined organic fractions were washed with brine (50 mL) and dried over anhydrous MgSO4. The solvents were evaporated, and the remaining oil was purified by flash chromatography over silica gel (0% to 10% EtOAc/hexanes) to afford 2.18 g (74%) of 3-bromo-5-methoxymethoxy-benzaldehyde (113b). was added the aqueous phase was extracted with Et2O (2×75 mL) The combined organic fractions were washed with brine (50 mL) dried over anhydrous MgSO4 The solvents were evaporated the remaining oil was purified by flash chromatography over silica gel (0% to 10% EtOAc/hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Chloromethylmethyl ether (1.45 mL, 19.13 mmol) was added dropwise to a solution of 3,5-dibromophenol (4.38 g, 17.39 mmol) and diisopropylethylamine (3.63 mL, 20.90 mmol) in CH2Cl2 (40 mL) at 0° C. The mixture was warmed to RT, stirred for 16 h, and added to H2O (50 mL). The layers were separated, and the aqueous fraction was extracted with CH2Cl2 (2×50 mL). The combined organic fractions were washed with brine (25 mL), dried over anhydrous MgSO4, and the solvent was evaporated to provide 5.20 g (100%) of 1,3-dibromo-5-methoxymethoxy-benzene (113a). The layers were separated the aqueous fraction was extracted with CH2Cl2 (2×50 mL) The combined organic fractions were washed with brine (25 mL) dried over anhydrous MgSO4 the solvent was evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Chloromethylmethyl ether (1.45 mL, 19.13 mmol) was added dropwise to a solution of 3,5-dibromophenol (4.38 g, 17.39 mmol) and diisopropylethylamine (3.63 mL, 20.90 mmol) in CH2Cl2 (40 mL) at 0° C. The mixture was warmed to RT, stirred for 16 h, and added to H2O (50 mL). The layers were separated, and the aqueous fraction was extracted with CH2Cl2 (2×50 mL). The combined organic fractions were washed with brine (25 mL), dried over anhydrous MgSO4, and the solvent was evaporated to provide 5.20 g (100%) of 1,3-dibromo-5-methoxymethoxy-benzene (113a). The layers were separated the aqueous fraction was extracted with CH2Cl2 (2×50 mL) The combined organic fractions were washed with brine (25 mL) dried over anhydrous MgSO4 the solvent was evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium hydride (693 mg, 17.33 mmol, 60%, oil was washed with pentane) in THF (15 mL) was added 3, 5-dibromophenol (3.0 g, 11.55 mmol) at 0° C. and the suspension was stirred for 30 minutes. Then, methoxymethyl chloride (1.4 g, 17.33 mmol) was added at 0° C. The resulting suspension was allowed to warm to room temperature and stirred for 2 days at which time TLC analysis of the mixture indicated the absence of starting material. Then, the reaction mixture was poured into an ice-water (50 mL) and the organic compound was extracted into ethyl acetate (2×100 mL). The combined extracts were washed with brine solution (250 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and the concentration of the solution under reduced pressure gave the crude residue which was purified by using an ISCO 120 g column chromatography, eluting with 5-20% ethyl acetate in hexanes to obtain 1,3-dibromo-5-methoxymethoxy-benzene (2.94 g, 86%) as a white solid: EI(+)-HRMS m/e calcd for C8H8Br2O2 (M)+ 293.8891, found 293.8893. stirred for 2 days at which time TLC analysis of the mixture the organic compound was extracted into ethyl acetate (2×100 mL) The combined extracts were washed with brine solution (250 mL) dried over anhydrous magnesium sulfate Filtration of the drying agent the concentration of the solution under reduced pressure gave the crude residue which was purified eluting with 5-20% ethyl acetate in hexanes

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of pyrrolidine (1.66 g, 23.27 mmol), in dry tetrahydrofuran (20 ml) was cooled to −78° C. under argon atmosphere. A solution of n-BuLi (15.5 ml, 1.5 M in hexanes) was added via slow drop-wise addition over 5 minutes. After complete addition the cooling bath was removed and the mixture allowed to warm to ice bath temperature over 30 minutes. A second oven dried flask was charged with 1,3-dibromo-5-methoxymethoxy-benzene (5.74 g, 19.4 mmol) and lithium bromide (1.68 g, 19.4 mmol) and taken up in dry tetrahydrofuran (10 ml). This flask was then cooled to 78° C. under argon. The contents of the first flask (slurry containing the lithio salt of pyrrolidine) was taken up in a syringe with wide bore needle and added via drop-wise addition to the second flask (over 10 minutes). The mixture was allowed to slowly warm to ambient temperature over night. The mixture was quenched via the addition of 1 N HCl (23 ml), saturated aqueous NH4Cl (34 ml) and water (40 ml). Ethyl acetate (80 ml) was added and the material shaken in a separtatory funnel. The ethyl acetate phase was collected and washed with an equal volume of 50% diluted brine solution. The aqueous phases were back extracted with ethyl acetate (2×50 ml), the organics combined, dried (MgSO4), filtered and stripped to provide a yellow remainder. The oil was purified by silica gel chromatography using 4%-8% EtOAc in hexanes as eluant to provide 930 mg of 1-(3-Bromo-5-methoxymethoxy-phenyl)-pyrrolidine as a light yellow mobile oil. After complete addition the cooling bath was removed to warm to ice bath temperature over 30 minutes A second oven dried flask was taken up in a syringe added via drop-wise addition to the second flask (over 10 minutes) to slowly warm to ambient temperature over night The mixture was quenched via the addition of 1 N HCl (23 ml), saturated aqueous NH4Cl (34 ml) and water (40 ml) Ethyl acetate (80 ml) was added The ethyl acetate phase was collected washed with an equal volume of 50% diluted brine solution The aqueous phases were back extracted with ethyl acetate (2×50 ml) dried (MgSO4) filtered to provide a yellow remainder The oil was purified by silica gel chromatography

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask was charged with sodium hydride (953 mg, 23.8 mmol, 60% in oil), in dry DMF (30 ml) and cooled to 0° C. (ice bath) under nitrogen atmosphere. 3,5-Dibromophenol (5 g, 19.9 mmol) was added in 4 equal portions over 10 minutes. After complete addition the cooling bath was removed and the mixture allowed to warm to ambient temperature over 20 minutes. Chloromethyl methyl ether (1.8 ml, 21.8 mmol) was added slowly, via syringe over about 5 minutes. The mixture was stirred over night. The material was quenched via the addition of saturated aqueous NH4Cl (20 ml) and all volatiles were stripped (rotovap/mechanical pump). The remainder was taken up in water (80 ml) and ethyl acetate (80 ml) and the material shaken in a separtatory funnel. The ethyl acetate phase was collected and washed with an equal volume of brine solution. The aqueous phases were back extracted with ethyl acetate (2×50 ml), the organics combined, dried (MgSO4), filtered and stripped to provide a crude oil. The oil was purified by silica gel chromatography using 4%-6% EtOAc in hexanes as eluant to provide 5.74 g of 1,3-dibromo-5-methoxymethoxy-benzene as a light yellow oil. After complete addition the cooling bath was removed to warm to ambient temperature over 20 minutes The material was quenched via the addition of saturated aqueous NH4Cl (20 ml) ethyl acetate (80 ml) and the material shaken in a separtatory funnel The ethyl acetate phase was collected washed with an equal volume of brine solution The aqueous phases were back extracted with ethyl acetate (2×50 ml) dried (MgSO4) filtered to provide a crude oil The oil was purified by silica gel chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: n-BuLi (8.34 mL of a 1.6 M solution in Et2O, 13.34 mmol) was added dropwise to a solution cooled to −78° C. of 1,3-dibromo-5-methoxymethoxy-benzene (3.59 g, 12.13 mmol) in anhydrous Et2O (40 mL) under a nitrogen atmosphere. The solution was aged at −78° C. for 45 m, anhydrous DMF (1.03 mL, 13.34 mmol) was added, and the reaction mixture was slowly warmed to RT. The mixture was poured into H2O (50 mL), and the aqueous phase was extracted with Et2O (2×75 mL). The combined organic fractions were washed with brine (50 mL) and dried over anhydrous MgSO4. The solvents were evaporated, and the remaining oil was purified by flash chromatography over silica gel (0% to 10% EtOAc/hexanes) to afford 2.18 g (74%) of 3-bromo-5-methoxymethoxy-benzaldehyde (113b). was added the aqueous phase was extracted with Et2O (2×75 mL) The combined organic fractions were washed with brine (50 mL) dried over anhydrous MgSO4 The solvents were evaporated the remaining oil was purified by flash chromatography over silica gel (0% to 10% EtOAc/hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Chloromethylmethyl ether (1.45 mL, 19.13 mmol) was added dropwise to a solution of 3,5-dibromophenol (4.38 g, 17.39 mmol) and diisopropylethylamine (3.63 mL, 20.90 mmol) in CH2Cl2 (40 mL) at 0° C. The mixture was warmed to RT, stirred for 16 h, and added to H2O (50 mL). The layers were separated, and the aqueous fraction was extracted with CH2Cl2 (2×50 mL). The combined organic fractions were washed with brine (25 mL), dried over anhydrous MgSO4, and the solvent was evaporated to provide 5.20 g (100%) of 1,3-dibromo-5-methoxymethoxy-benzene (113a). The layers were separated the aqueous fraction was extracted with CH2Cl2 (2×50 mL) The combined organic fractions were washed with brine (25 mL) dried over anhydrous MgSO4 the solvent was evaporated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium hydride (693 mg, 17.33 mmol, 60%, oil was washed with pentane) in THF (15 mL) was added 3, 5-dibromophenol (3.0 g, 11.55 mmol) at 0° C. and the suspension was stirred for 30 minutes. Then, methoxymethyl chloride (1.4 g, 17.33 mmol) was added at 0° C. The resulting suspension was allowed to warm to room temperature and stirred for 2 days at which time TLC analysis of the mixture indicated the absence of starting material. Then, the reaction mixture was poured into an ice-water (50 mL) and the organic compound was extracted into ethyl acetate (2×100 mL). The combined extracts were washed with brine solution (250 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and the concentration of the solution under reduced pressure gave the crude residue which was purified by using an ISCO 120 g column chromatography, eluting with 5-20% ethyl acetate in hexanes to obtain 1,3-dibromo-5-methoxymethoxy-benzene (2.94 g, 86%) as a white solid: EI(+)-HRMS m/e calcd for C8H8Br2O2 (M)+ 293.8891, found 293.8893. stirred for 2 days at which time TLC analysis of the mixture the organic compound was extracted into ethyl acetate (2×100 mL) The combined extracts were washed with brine solution (250 mL) dried over anhydrous magnesium sulfate Filtration of the drying agent the concentration of the solution under reduced pressure gave the crude residue which was purified eluting with 5-20% ethyl acetate in hexanes