反応 #657332

反応方程式

piperidin-4-yl-carbamic acid benzyl ester

potassium carbonate

potassium iodide

(3-bromo-propyl)-carbamic acid tert-butyl ester

→

title compound

[1-(3-tert-Butoxycarbonylamino-propyl)-piperidin-4-yl]-carbamic acid benzyl ester

溶媒

dimethylformamide

反応条件

後処理

1. 1
   温度After 90 min at 60° C. the reaction mixture was cooled to 23° C.
2. 2
   その他then partitioned between ethyl acetate and water (100 mL each)
3. 3
   その他The organic layer was separated
4. 4
   洗浄washed with saturated brine solution (150 mL)
5. 5
   乾燥dried (MgSO4)
6. 6
   ろ過filtered
7. 7
   濃縮concentrated
8. 8
   その他The product was purified
9. 9
   洗浄then eluted with 2 M ammonia in methanol in dichloromethane (0-12.5% 2 M ammonia in methanol linear gradient over 12 column volumes at a flow rate of 100 mL/min)

実験手順

To a solution of piperidin-4-yl-carbamic acid benzyl ester (15 g, 58.4 mmol, crude product from Boc-deprotection step) in dimethylformamide (60 mL) at 23° C. was added potassium carbonate (12.1 g, 87.6 mmol, 1.5 equiv), potassium iodide (4.85 g, 29.2 mmol, 0.5 equiv) and (3-bromo-propyl)-carbamic acid tert-butyl ester (13.9 g, 58.4 mmol, 1 equiv). The resulting mixture was warmed to 60° C. (oil bath). After 90 min at 60° C. the reaction mixture was cooled to 23° C. then partitioned between ethyl acetate and water (100 mL each). The organic layer was separated, washed with saturated brine solution (150 mL), dried (MgSO4), filtered and concentrated. The product was purified using an Isco CombiFlash automated chromatography system. The residue was loaded onto a 330 g silica gel column as a solution in dichloromethane (25 mL) then eluted with 2 M ammonia in methanol in dichloromethane (0-12.5% 2 M ammonia in methanol linear gradient over 12 column volumes at a flow rate of 100 mL/min) to give 16.9 g (43.2 mmol, 74% over 3 steps) of the title compound as a clear

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