tert-butyl 4-fluoro-4-(methylsulfonyloxymethyl)piperidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (0.050 g, 0.149 mmol) was dissolved in DMA (0.5 mL) and treated with Cs2CO3 (0.097 g, 0.29 mmol). After stirring for several minutes, tert-butyl 4-fluoro-4-((methylsulfonyloxy)methyl)piperidine-1-carboxylate (0.053 g, 0.171 mmol) was added. The mixture was heated to 90° C. for 40 hours. The entire reaction mixture was applied to a SiO2 column and eluted with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate to provide the desired product (11 mg). MS ESI (+) m/z 551.1 (M+1) detected. The entire reaction mixture eluted with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (0.050 g, 0.149 mmol) was dissolved in DMA (0.5 mL) and treated with Cs2CO3 (0.097 g, 0.29 mmol). After stirring for several minutes, tert-butyl 4-fluoro-4-((methylsulfonyloxy)methyl)piperidine-1-carboxylate (0.053 g, 0.171 mmol) was added. The mixture was heated to 90° C. for 40 hours. The entire reaction mixture was applied to a SiO2 column and eluted with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate to provide the desired product (11 mg). MS ESI (+) m/z 551.1 (M+1) detected. The entire reaction mixture eluted with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: tert-Butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (0.150 g, 0.643 mmol) was dissolved in dichloromethane (1.8 mL) and cooled to 0° C. The solution was treated with triethylamine (0.134 ml, 0.964 mmol) followed by methanesulfonyl chloride (0.0547 ml, 0.707 mmol). The reaction was stirred at 0° C. for 2 hours then diluted with methylene chloride and quenched with saturated NH4Cl and separated. The organic layer was washed with saturated NH4Cl, 6% NaHCO3, dried over Na2SO4, filtered and concentrated in vacuo to provide the desired product (200 mg). quenched with saturated NH4Cl separated The organic layer was washed with saturated NH4Cl, 6% NaHCO3 dried over Na2SO4 filtered concentrated in vacuo

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

Procedure: To a 0° C. solution of tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (2.60 g, 11.1 mmol) and triethylamine (2.33 mL, 16.7 mmol) in 55 mL dichloromethane was added neat methanesulfonyl chloride (0.949 mL, 12.3 mmol) dropwise by syringe. The reaction mixture was slowly warmed to ambient temperature and stirred at ambient temperature for 17 hours. Saturated NaHCO3 was added, the mixture was extracted with dichloromethane, and combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to give the title compound (3.2 g, 92.2% yield) as a white powder. the mixture was extracted with dichloromethane were dried (Na2SO4) filtered concentrated The crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate)

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

Procedure: To a 0° C. solution of tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (2.60 g, 11.1 mmol) and triethylamine (2.33 mL, 16.7 mmol) in 55 mL dichloromethane was added neat methanesulfonyl chloride (0.949 mL, 12.3 mmol) dropwise by syringe. The reaction mixture was slowly warmed to ambient temperature and stirred at ambient temperature for 17 hours. Saturated NaHCO3 was added, the mixture was extracted with dichloromethane, and combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to give the title compound (3.2 g, 92.2% yield) as a white powder. the mixture was extracted with dichloromethane were dried (Na2SO4) filtered concentrated The crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a 0° C. solution of tert-butyl 4-fluoro-4-(hydroxymethyl)piperidine-1-carboxylate (2.60 g, 11.1 mmol) and triethylamine (2.33 mL, 16.7 mmol) in 55 mL dichloromethane was added neat methanesulfonyl chloride (0.949 mL, 12.3 mmol) dropwise by syringe. The reaction mixture was slowly warmed to ambient temperature and stirred at ambient temperature for 17 hours. Saturated NaHCO3 was added, the mixture was extracted with dichloromethane, and combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate) to give the title compound (3.2 g, 92.2% yield) as a white powder. the mixture was extracted with dichloromethane were dried (Na2SO4) filtered concentrated The crude was purified on silica gel (4:1 hexanes:ethyl acetate to 1:1 hexanes:ethyl acetate)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(7-(2-Methoxyethoxy)imidazo[1,2-a]pyridin-3-yl)quinolin-8-ol (0.050 g, 0.149 mmol) was dissolved in DMA (0.5 mL) and treated with Cs2CO3 (0.097 g, 0.29 mmol). After stirring for several minutes, tert-butyl 4-fluoro-4-((methylsulfonyloxy)methyl)piperidine-1-carboxylate (0.053 g, 0.171 mmol) was added. The mixture was heated to 90° C. for 40 hours. The entire reaction mixture was applied to a SiO2 column and eluted with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate to provide the desired product (11 mg). MS ESI (+) m/z 551.1 (M+1) detected. The entire reaction mixture eluted with a gradient from 1-20% (6% NH4OH in MeOH)/ethyl acetate