4-(2-hydroxyethyl)piperidin-4-ol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of compound 25 (1.32 g, 5.30 mmol) in methanol (10 mL) under argon was added palladium hydroxide (20%) on activated charcoal (132 mg, 10% w/w). The solution was purged three times with hydrogen and stirred under hydrogen atmosphere at 60° C. for 4 hrs. The resulting solution was then filtered on celite plug to give desired compound 26 (790 mg, 94%) which was used as such for the next step. The solution was purged three times with hydrogen The resulting solution was then filtered on celite plug

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of compound 26 (517 mg, 3.25 mmol) in anhydrous dimethylformamide (15 mL) under argon were added triethylamine (1.32 g, 13.0 mmol) and 4-fluoro-2-trifluoromethylbenzonitrile (1.80 g, 9.52 mmol). The solution was stirred at 80° C. for 4 hrs. The solution was cooled at room temperature and poured in water (100 mL), extracted with diethyl ether (3×25 mL), washed with brine and finally dried over magnesium sulphate. Purification of the resulting crude product by flash chromatography using ethyl acetate/hexane (7:3) as an eluant gave the desired compound 27a (687 mg, 68%). 1H NMR (400 MHz, Acetone-d6) δ: 1.74 (m, 6H), 3.45 (m, 2H), 3.85 (m, 4H), 7.24 (dd, 1H, J1=6.4 Hz, J2 =2.5 Hz), 7.32 (d, 1H, J=2.4 Hz), 7.72 (d, 1H, J=8.8 Hz). The solution was cooled at room temperature extracted with diethyl ether (3×25 mL) washed with brine finally dried over magnesium sulphate Purification of the resulting crude product by flash chromatography

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of compound 26 (517 mg, 3.25 mmol) in anhydrous dimethylformamide (15 mL) under argon were added triethylamine (1.32 g, 13.0 mmol) and 4-fluoro-2-trifluoromethylbenzonitrile (1.80 g, 9.52 mmol). The solution was stirred at 80° C. for 4 hrs. The solution was cooled at room temperature and poured in water (100 mL), extracted with diethyl ether (3×25 mL), washed with brine and finally dried over magnesium sulphate. Purification of the resulting crude product by flash chromatography using ethyl acetate/hexane (7:3) as an eluant gave the desired compound 27a (687 mg, 68%). 1H NMR (400 MHz, Acetone-d6) δ: 1.74 (m, 6H), 3.45 (m, 2H), 3.85 (m, 4H), 7.24 (dd, 1H, J1=6.4 Hz, J2=2.5 Hz), 7.32 (d, 1H, J=2.4 Hz), 7.72 (d, 1H, J=8.8 Hz). The solution was cooled at room temperature extracted with diethyl ether (3×25 mL) washed with brine finally dried over magnesium sulphate Purification of the resulting crude product by flash chromatography

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of compound 25 (1.32 g, 5.30 mmol) in methanol (10 mL) under argon was added palladium hydroxide (20%) on activated charcoal (132 mg, 10% w/w). The solution was purged three times with hydrogen and stirred under hydrogen atmosphere at 60° C. for 4 hrs. The resulting solution was then filtered on celite plug to give desired compound 26 (790 mg, 94%) which was used as such for the next step. The solution was purged three times with hydrogen The resulting solution was then filtered on celite plug