1-[4-(hydroxymethyl)piperidin-1-yl]ethanone

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-one (200 mg) and THF (4 ml) were mixed, and NaH (70 mg) was added thereto, followed by stirring at room temperature for minutes. 5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine (200 mg) was added to the reaction mixture, followed by stirring at room temperature for 1 hour, and then 1 M TBAF/THF (1.2 ml) was added thereto, followed by stirring at room temperature. Water and EtOAc were added to the reaction mixture, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH) to obtain 1-{4-[({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-one (167 mg). by stirring at room temperature for 1 hour by stirring at room temperature the organic layer was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-one (200 mg) and THF (4 ml) were mixed, and NaH (70 mg) was added thereto, followed by stirring at room temperature for minutes. 5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine (200 mg) was added to the reaction mixture, followed by stirring at room temperature for 1 hour, and then 1 M TBAF/THF (1.2 ml) was added thereto, followed by stirring at room temperature. Water and EtOAc were added to the reaction mixture, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH) to obtain 1-{4-[({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-one (167 mg). by stirring at room temperature for 1 hour by stirring at room temperature the organic layer was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-one (200 mg) and THF (4 ml) were mixed, and NaH (70 mg) was added thereto, followed by stirring at room temperature for 10 minutes. 5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine (200 mg) was added to the reaction mixture, followed by stirring at room temperature for 1 hour, and then 1M TBAF/THF (1.2 ml) was added thereto, followed by stirring at room temperature. Water and EtOAc were added to the reaction mixture, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH) to obtain 1-{4-[({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}e than-1-one (167 mg). by stirring at room temperature for 1 hour by stirring at room temperature the organic layer was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Acetyl-4-hydroxymethylpiperidine may be obtained in the following manner: acetic anhydride (20.5 cc) is added in the course of 15 minutes to a solution of hydroxymethylpiperidine (23.8 g) in ethanol (100 cc) at a temperature in the region of 10° C., and the mixture is stirred for 18 hours at a temperature in the region of 20° C. The reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa); the residue obtained is taken up with water (50 cc) and potassium carbonate (50 g), and the solution is extracted with methylene chloride (3×150 cc); the organic extracts are combined, dried and concentrated to dryness under reduced pressure (2.7 kPa). 1-Acetyl-4-hydroxymethylpiperidine (33.6 g) is thereby obtained in the form of an oil, which is employed in the crude state in the subsequent syntheses. The reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) the residue obtained the solution is extracted with methylene chloride (3×150 cc) dried concentrated to dryness under reduced pressure (2.7 kPa)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The title compound is prepared analogously as described for N-(2-hydroxy-1,1-dimethyl-ethyl)-acetamide from piperidin-4-yl-methanol. MS (LC-MS): [M+H]+=158.3. tR (HPLC, Waters Symmetry C18 column, 5-95% CH3CN/H2O/3.5 min, 95% CH3CN/H2O, 2 min, CH3CN and H2O containing 0.1% TFA, flow: 0.6 mL/min): 0.39 min. 0.39 min.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-[4-(Hydroxymethyl)piperidin-1-yl]ethan-1-one (200 mg) and THF (4 ml) were mixed, and NaH (70 mg) was added thereto, followed by stirring at room temperature for minutes. 5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-chloropyrimidine (200 mg) was added to the reaction mixture, followed by stirring at room temperature for 1 hour, and then 1 M TBAF/THF (1.2 ml) was added thereto, followed by stirring at room temperature. Water and EtOAc were added to the reaction mixture, and the organic layer was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH) to obtain 1-{4-[({5-[2-fluoro-3-(hydroxymethyl)phenyl]pyrimidin-2-yl}oxy)methyl]piperidin-1-yl}ethan-1-one (167 mg). by stirring at room temperature for 1 hour by stirring at room temperature the organic layer was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane/EtOAc/CHCl3/MeOH)