N-[(4-bromophenyl)methyl]-2,2-dimethoxyethanamine

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

Procedure: Starting from 4-Bromo-3-chloro-benzaldehyde, the title compound was prepared by the method described for (4-Bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1). Rt=0.94 min (Method C). Detected mass: 308.3/310.3 (M+H+).

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

Procedure: 60.5 g (4-Bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1, crude product) were dissolved in 270 ml of dichloromethane/pyridine (8:1). At 0° C. a solution of 76.0 g (386.4 mmol) p-toluenesulfonylchloride in 100 ml of dichloromethane was added and the solution was stirred at room temperature. After 3 h, the reaction mixture was washed twice with 2 N HCl and saturated sodium hydrogen carbonate-solution. The organic layer was dried over magnesium sulfate and evaporated. Final silica gel chromatography (heptane/ethylacetate 4:1) gave 59.9 g of the title compound. Rt=1.82 min (Method C). Detected mass: 396.1/398.1 (M−OMe−). the reaction mixture was washed twice with 2 N HCl and saturated sodium hydrogen carbonate-solution The organic layer was dried over magnesium sulfate evaporated

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

Procedure: 50 g (270.2 mmol) 4-bromobenzaldehyde were dissolved in 200 ml of toluene and 28.4 g (270.2 mmol) aminoacetaldehyde dimethylacetal were added. After the addition of 5.1 g (27.0 mmol) p-toluenesulfonic acid monohydrate, the reaction mixture was heated under reflux in a Dean Stark apparatus. After 4 h, the reaction was cooled to room temperature and washed with saturated sodium hydrogen carbonate-solution (2×) and water. The combined aqueous layers were extracted with Toluene and the combined organic layers were dried over magnesium sulfate and evaporated. The residue was dissolved in 200 ml of ethanol and 5.11 g (135.1 mmol) of sodium borohydride were added in small portions. After stirring for 2 h at room temperature and standing overnight, 5.0 ml acetic acid were added and the solvent was removed i. vac. The residue was taken up in dichloromethane and washed (2×) with water. After drying over magnesium sulfate and evaporation, 60.5 g of the title compound were obtained (crude product), which were used without further purification. Rt=0.80 min (Method C). Detected mass: 274.1/276.1 (M+H+). the reaction mixture was heated under reflux in a Dean Stark apparatus washed with saturated sodium hydrogen carbonate-solution (2×) and water The combined aqueous layers were extracted with Toluene the combined organic layers were dried over magnesium sulfate evaporated The residue was dissolved in 200 ml of ethanol standing overnight the solvent was removed i washed (2×) with water After drying over magnesium sulfate and evaporation

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of N-(4-bromobenzyl)-2,2-dimethoxyethanamine (10 g, 0.037 mol) in CH2Cl2 (100 mL) was added ClSO3H (21.3 g, 0.18 mol) at −20° C. dropwise. The resulting reaction mixture was allowed to stir at 45° C. for 10 h. The resulting reaction mixture was diluted with CH2Cl2 and ice cold H2O, then neutralized with aqueous NaHCO3. The organic layer was separated and aqueous layer extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated at reduced pressure to get crude 6-bromoisoquinoline, which was purified by silica gel chromatography eluting with 5-15% EtOAc-hexanes to afford 6-bromoisoquinoline (0.9 g, 12%) as yellow liquid. The resulting reaction mixture The resulting reaction mixture The organic layer was separated aqueous layer extracted with CH2Cl2 The combined organic layers were dried over Na2SO4 concentrated at reduced pressure

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of N-(4-bromobenzyl)-2,2-dimethoxyethanamine (10 g, 0.037 mol) in CH2Cl2 (100 mL) was added ClSO3H (21.3 g, 0.18 mol) at −20° C. dropwise. The resulting reaction mixture was allowed to stir at 45° C. for 10 h. The resulting reaction mixture was diluted with CH2Cl2 and ice cold H2O, then neutralized with aqueous NaHCO3. The organic layer was separated and aqueous layer extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated at reduced pressure to get crude 6-bromoisoquinoline, which was purified by silica gel chromatography eluting with 5-15% EtOAc-hexanes to afford 6-bromoisoquinoline (0.9 g, 12%) as yellow liquid. The resulting reaction mixture The resulting reaction mixture The organic layer was separated aqueous layer extracted with CH2Cl2 The combined organic layers were dried over Na2SO4 concentrated at reduced pressure

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

Procedure: To an ice-cold solution of 4-bromo-benzaldehyde (10 g, 0.05 mol) and 2,2-dimethoxy-ethylamine (6.8 g, 0.06 mol) in MeOH (200 mL) was added AcOH (2 mL), and the reaction mixture was stirred at RT for 1 h. The reaction mixture was cooled to 0° C. and NaBH4 (6.2 g, 0.15 mol) was added portionwise. The reaction mixture was stirred at RT for 10 h. After completion, The resulting reaction mixture was concentrated under reduced pressure and 10% aqueous NaOH was added. The mixture was extracted with EtOAc, the organic layer separated, dried over Na2SO4, and concentrated under reduced pressure. Purification was done by column chromatography using 100-200 mesh silica gel eluting with 5-15% EtOAc in hexanes to afford N-(4-bromobenzyl)-2,2-dimethoxyethanamine (10 g, 67%) as a pale yellow liquid. The reaction mixture was cooled to 0° C. The reaction mixture was stirred at RT for 10 h After completion, The resulting reaction mixture was concentrated under reduced pressure and 10% aqueous NaOH was added The mixture was extracted with EtOAc the organic layer separated dried over Na2SO4 concentrated under reduced pressure Purification

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

Procedure: Starting from 4-Bromo-3-chloro-benzaldehyde, the title compound was prepared by the method described for (4-Bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1). Rt=0.94 min (Method C). Detected mass: 308.3/310.3 (M+H+).

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

Procedure: 60.5 g (4-Bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1, crude product) were dissolved in 270 ml of dichloromethane/pyridine (8:1). At 0° C. a solution of 76.0 g (386.4 mmol) p-toluenesulfonylchloride in 100 ml of dichloromethane was added and the solution was stirred at room temperature. After 3 h, the reaction mixture was washed twice with 2 N HCl and saturated sodium hydrogen carbonate-solution. The organic layer was dried over magnesium sulfate and evaporated. Final silica gel chromatography (heptane/ethylacetate 4:1) gave 59.9 g of the title compound. Rt=1.82 min (Method C). Detected mass: 396.1/398.1 (M−OMe−). the reaction mixture was washed twice with 2 N HCl and saturated sodium hydrogen carbonate-solution The organic layer was dried over magnesium sulfate evaporated

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

Procedure: 50 g (270.2 mmol) 4-bromobenzaldehyde were dissolved in 200 ml of toluene and 28.4 g (270.2 mmol) aminoacetaldehyde dimethylacetal were added. After the addition of 5.1 g (27.0 mmol) p-toluenesulfonic acid monohydrate, the reaction mixture was heated under reflux in a Dean Stark apparatus. After 4 h, the reaction was cooled to room temperature and washed with saturated sodium hydrogen carbonate-solution (2×) and water. The combined aqueous layers were extracted with Toluene and the combined organic layers were dried over magnesium sulfate and evaporated. The residue was dissolved in 200 ml of ethanol and 5.11 g (135.1 mmol) of sodium borohydride were added in small portions. After stirring for 2 h at room temperature and standing overnight, 5.0 ml acetic acid were added and the solvent was removed i. vac. The residue was taken up in dichloromethane and washed (2×) with water. After drying over magnesium sulfate and evaporation, 60.5 g of the title compound were obtained (crude product), which were used without further purification. Rt=0.80 min (Method C). Detected mass: 274.1/276.1 (M+H+). the reaction mixture was heated under reflux in a Dean Stark apparatus washed with saturated sodium hydrogen carbonate-solution (2×) and water The combined aqueous layers were extracted with Toluene the combined organic layers were dried over magnesium sulfate evaporated The residue was dissolved in 200 ml of ethanol standing overnight the solvent was removed i washed (2×) with water After drying over magnesium sulfate and evaporation

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

Procedure: 50 g (270.2 mmol) 4-bromobenzaldehyde were dissolved in 200 ml of toluene and 28.4 g (270.2 mmol) aminoacetaldehyde dimethylacetal were added. After the addition of 5.1 g (27.0 mmol) p-toluenesulfonic acid monohydrate, the reaction mixture was heated under reflux in a Dean Stark apparatus. After 4 h, the reaction was cooled to room temperature and washed with saturated sodium hydrogen carbonate-solution (2×) and water. The combined aqueous layers were extracted with Toluene and the combined organic layers were dried over magnesium sulfate and evaporated. The residue was dissolved in 200 ml of ethanol and 5.11 g (135.1 mmol) of sodium borohydride were added in small portions. After stirring for 2 h at room temperature and standing overnight, 5.0 ml acetic acid were added and the solvent was removed i. vac. The residue was taken up in dichloromethane and washed (2×) with water. After drying over magnesium sulfate and evaporation, 60.5 g of the title compound were obtained (crude product), which were used without further purification. Rt=0.80 min (Method C). Detected mass: 274.1/276.1 (M+H+). the reaction mixture was heated under reflux in a Dean Stark apparatus washed with saturated sodium hydrogen carbonate-solution (2×) and water The combined aqueous layers were extracted with Toluene the combined organic layers were dried over magnesium sulfate evaporated The residue was dissolved in 200 ml of ethanol standing overnight the solvent was removed i washed (2×) with water After drying over magnesium sulfate and evaporation

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

Procedure: 60.5 g (4-bromo-benzyl)-(2,2-dimethoxy-ethyl)-amine (1, crude product) were dissolved in 270 ml dichloromethane/pyridine (8:1). At 0° C. a solution of 76.0 g (386.4 mmol) p-toluenesulfonylchloride in 100 ml dichloromethane were added and the solution was stirred at room temperature. After 3 h, the reaction mixture was washed twice with 2 N HCl and saturated NaHCO3-solution. The organic layer was dried with MgSO4 and evaporated. Final silicagel chromatography (heptane/ethyl acetate 4:1) gave 59.9 g of the title compound. Rt=1.82 min (Method C). Detected mass: 396.1/398.1 (M-OMe−). the reaction mixture was washed twice with 2 N HCl and saturated NaHCO3-solution The organic layer was dried with MgSO4 evaporated

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

Procedure: 50 g (270.2 mmol) 4-bromobenzaldehyde were dissolved in 200 ml toluene and 28.4 g (270.2 mmol) aminoacetaldehyde dimethylacetal were added. After the addition of 5.1 g (27.0 mmol) p-toluenesulfonic acid monohydrate, the reaction mixture was heated under reflux in a Dean Stark apparatus. After 4 h, the reaction was cooled to room temperature and washed with saturated NaHCO3-solution (2×) and H2O. The combined aqueous layers were extracted with toluene and the combined organic layers were dried with MgSO4 and evaporated. The residue was dissolved in 200 ml ethanol and 5.11 g (135.1 mmol) sodium borohydride were added in small portions. After stirring for 2 h at room temperature and standing overnight, 5.0 ml acetic acid were added and the solvent was removed i. vac. The residue was taken up in dichloromethane and washed (2×) with H2O. After drying with MgSO4 and evaporation, 60.5 g of the title compound were obtained, which were used without further purification. Rt=0.80 min (Method C). Detected mass: 274.1/276.1 (M+H+). the reaction mixture was heated under reflux in a Dean Stark apparatus washed with saturated NaHCO3-solution (2×) and H2O The combined aqueous layers were extracted with toluene the combined organic layers were dried with MgSO4 evaporated The residue was dissolved in 200 ml ethanol standing overnight the solvent was removed i washed (2×) with H2O After drying with MgSO4 and evaporation