tert-butyl-dimethyl-(piperidin-4-ylmethoxy)silane

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloropyridine (1.00 g, 5.20 mmol), 4-((t-butyldimethylsilyloxy)-methyl)piperidine (284), (1.19 g, 5.20 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0952 g, 0.104 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.180 g, 0.312 mmol), and sodium t-butoxide (0.749 g, 7.79 mmol) were dissolved in 40 mL dioxane under argon. The reaction was heated at 80° C. for 17 hours. The resulting solution was cooled an taken up in ethyl acetate (125 mL) and washed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate) afforded compound 281 as a white solid (158 mg, 9%). The resulting solution was cooled washed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL) The organic phase was dried (MgSO4) evaporated to give an orange oil Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloropyridine (1.00 g, 5.20 mmol), 4-((t-butyldimethylsilyloxy)-methyl)piperidine (284), (1.19 g, 5.20 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0952 g, 0.104 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.180 g, 0.312 mmol), and sodium t-butoxide (0.749 g, 7.79 mmol) were dissolved in 40 mL dioxane under argon. The reaction was heated at 80° C. for 17 hours. The resulting solution was cooled an taken up in ethyl acetate (125 mL) and washed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate) afforded compound 281 as a white solid (158 mg, 9%). The resulting solution was cooled washed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL) The organic phase was dried (MgSO4) evaporated to give an orange oil Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate)

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

Procedure: Piperidin-4-ylmethanol (2.50 g, 21.7 mmol), t-butylchlorodimethylsilane (4.13 g, 23.9 mmol), and imidazole (1.48 g, 21.7 mmol) were dissolved in dichloromethane (25 mL) and stirred at room temperature for 18 hours. The reaction was added to aqueous NaHCO3 (200 mL, 50% saturated) and extracted with dichloromethane (3×150 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow oil. Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) gave a soft white solid, which was then added to 0.5 M NaOH (100 mL) and extracted with dichloromethane+10% methanol (3×100 mL). The combined organics were dried (MgSO4) and evaporated to give compound 284 as a pale yellow oil (4.75 g). extracted with dichloromethane (3×150 mL) The combined organics were dried (MgSO4) evaporated to give a yellow oil Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) gave a soft white solid, which extracted with dichloromethane+10% methanol (3×100 mL) The combined organics were dried (MgSO4) evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloropyridine (1.00 g, 5.20 mmol), 4-((t-butyldimethylsilyloxy)-methyl)piperidine (284), (1.19 g, 5.20 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0952 g, 0.104 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.180 g, 0.312 mmol), and sodium t-butoxide (0.749 g, 7.79 mmol) were dissolved in 40 mL dioxane under argon. The reaction was heated at 80° C. for 17 hours. The resulting solution was cooled an taken up in ethyl acetate (125 mL) and washed with aqueous K2CO3, (10%, 100 mL) water (100 mLl), and brine (100 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate) afforded compound 281 as a white solid (158 mg, 9%). The resulting solution was cooled washed with aqueous K2CO3, (10%, 100 mL) water (100 mLl), and brine (100 mL) The organic phase was dried (MgSO4) evaporated to give an orange oil Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate)

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

Procedure: Piperidin-4-ylmethanol (2.50 g, 21.7 mmol), t-butylchlorodimethylsilane (4.13 g, 23.9 mmol), and imidazole (1.48 g, 21.7 mmol) were dissolved in dichloromethane (25 mL) and stirred at room temperature for 18 hours. The reaction was added to aqueous NaHCO3 (200 mL, 50% saturated) and extracted with dichloromethane (3×150 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow oil. Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) gave a soft white solid, which was then added to 0.5 M NaOH (100 mL) and extracted with dichloromethane+10% methanol (3×100 mL). The combined organics were dried (MgSO4) and evaporated to give compound 284 as a pale yellow oil (4.75 g). extracted with dichloromethane (3×150 mL) The combined organics were dried (MgSO4) evaporated to give a yellow oil Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) gave a soft white solid, which extracted with dichloromethane+10% methanol (3×100 mL) The combined organics were dried (MgSO4) evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-Bromo-2-chloropyridine (1.00 g, 5.20 mmol), 4-((t-butyldimethylsilyloxy)-methyl)piperidine (284), (1.19 g, 5.20 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.0952 g, 0.104 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethyl-9H-xanthene (0.180 g, 0.312 mmol), and sodium t-butoxide (0.749 g, 7.79 mmol) were dissolved in 40 mL dioxane under argon. The reaction was heated at 80° C. for 17 hours. The resulting solution was cooled an taken up in ethyl acetate (125 mL) and washed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL). The organic phase was dried (MgSO4) and evaporated to give an orange oil. Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate) afforded compound 281 as a white solid (158 mg, 9%). The resulting solution was cooled washed with aqueous K2CO3, (10%, 100 mL) water (100 mL1), and brine (100 mL) The organic phase was dried (MgSO4) evaporated to give an orange oil Silica gel chromatography (gradient elution hexanes/0-10% ethyl acetate)

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

Procedure: Piperidin-4-ylmethanol (2.50 g, 21.7 mmol), t-butylchlorodimethylsilane (4.13 g, 23.9 mmol), and imidazole (1.48 g, 21.7 mmol) were dissolved in dichloromethane (25 mL) and stirred at room temperature for 18 hours. The reaction was added to aqueous NaHCO3 (200 mL, 50% saturated) and extracted with dichloromethane (3×150 mL). The combined organics were dried (MgSO4) and evaporated to give a yellow oil. Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) gave a soft white solid, which was then added to 0.5 M NaOH (100 mL) and extracted with dichloromethane+10% methanol (3×100 mL). The combined organics were dried (MgSO4) and evaporated to give compound 284 as a pale yellow oil (4.75 g). extracted with dichloromethane (3×150 mL) The combined organics were dried (MgSO4) evaporated to give a yellow oil Silica gel chromatography (gradient elution dichloromethane+2.5% TEA/0-10% methanol) gave a soft white solid, which extracted with dichloromethane+10% methanol (3×100 mL) The combined organics were dried (MgSO4) evaporated