4-[3-(4-bromophenyl)propyl]morpholine

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of lithium aluminum hydride (4.4 g, 115.79 mmol, 2.00 equiv) in tetrahydrofuran (120 mL) maintained under nitrogen at −30° C. was added a solution of 3-(4-bromophenyl)-1-morpholinopropan-1-one (17.2 g, 57.91 mmol, 1.00 equiv) in tetrahydrofuran (80 mL) dropwise with stirring. The resulting solution was stirred at −30° C. for 30 min and at room temperature for 2 h. The reaction was quenched by the sequential addition of 4.4 mL of water, 13 mL of 15% aqueous sodium hydroxide solution and 4.4 mL of water. The solid was removed by filtration and the filtrate was extracted with 1×350 mL of ethyl acetate. The organic layer was washed with 2×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 13.5 g (82%) of 4-(3-(4-bromophenyl)propyl)morpholine as a light yellow oil. The resulting solution was stirred at −30° C. for 30 min and at room temperature for 2 h The reaction was quenched by the sequential addition of 4.4 mL of water, 13 mL of 15% aqueous sodium hydroxide solution and 4.4 mL of water The solid was removed by filtration the filtrate was extracted with 1×350 mL of ethyl acetate The organic layer was washed with 2×50 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of lithium aluminum hydride (4.4 g, 115.79 mmol, 2.00 equiv) in tetrahydrofuran (120 mL) maintained under nitrogen at −30° C. was added a solution of 3-(4-bromophenyl)-1-morpholinopropan-1-one (17.2 g, 57.91 mmol, 1.00 equiv) in tetrahydrofuran (80 mL) dropwise with stirring. The resulting solution was stirred at −30° C. for 30 min and at room temperature for 2 h. The reaction was quenched by the sequential addition of 4.4 mL of water, 13 mL of 15% aqueous sodium hydroxide solution and 4.4 mL of water. The solid was removed by filtration and the filtrate was extracted with 1×350 mL of ethyl acetate. The organic layer was washed with 2×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 13.5 g (82%) of 4-(3-(4-bromophenyl)propyl)morpholine as a light yellow oil. The resulting solution was stirred at −30° C. for 30 min and at room temperature for 2 h The reaction was quenched by the sequential addition of 4.4 mL of water, 13 mL of 15% aqueous sodium hydroxide solution and 4.4 mL of water The solid was removed by filtration the filtrate was extracted with 1×350 mL of ethyl acetate The organic layer was washed with 2×50 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum

Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of lithium aluminum hydride (4.4 g, 115.79 mmol, 2.00 equiv) in tetrahydrofuran (120 mL) maintained under nitrogen at −30° C. was added a solution of 3-(4-bromophenyl)-1-morpholinopropan-1-one (17.2 g, 57.91 mmol, 1.00 equiv) in tetrahydrofuran (80 mL) dropwise with stirring. The resulting solution was stirred at −30° C. for 30 min and at room temperature for 2 h. The reaction was quenched by the sequential addition of 4.4 mL of water, 13 mL of 15% aqueous sodium hydroxide solution and 4.4 mL of water. The solid was removed by filtration and the filtrate was extracted with 1×350 mL of ethyl acetate. The organic layer was washed with 2×50 mL of brine, dried over anhydrous sodium sulfate and concentrated under vacuum to afford 13.5 g (82%) of 4-(3-(4-bromophenyl)propyl)morpholine as a light yellow oil. The resulting solution was stirred at −30° C. for 30 min and at room temperature for 2 h The reaction was quenched by the sequential addition of 4.4 mL of water, 13 mL of 15% aqueous sodium hydroxide solution and 4.4 mL of water The solid was removed by filtration the filtrate was extracted with 1×350 mL of ethyl acetate The organic layer was washed with 2×50 mL of brine dried over anhydrous sodium sulfate concentrated under vacuum

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane

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

Procedure: A solution of Example 4B (760 mg, 2.550 mmol) in THF (10 mL) at room temperature was treated with 5M BH3/dimethylsulfide in diethyl ether (2.55 mL, 12.752 mmol), stirred for 24 hours, treated with 3N aqueous HCl (10 mL), heated to reflux for 1 hour, and partitioned between ethyl acetate and 1N NaOH. The aqueous layer was extracted with ethyl acetate (3×50 mL) and the combined extracts were dried (MgSO4), filtered, and concentrated. The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane to provide the desired product (565 mg, 78%). heated to reflux for 1 hour partitioned between ethyl acetate and 1N NaOH The aqueous layer was extracted with ethyl acetate (3×50 mL) the combined extracts were dried (MgSO4) filtered concentrated The concentrate was purified by flash column chromatography on silica gel with 5% 2N NH3 in methanol/dichloromethane