Acetic Acid → 1-Cyclopropyl-4-(4-nitrophenyl)piperidine

関与物質

反応手順

4-(4-Nitrophenyl)piperidine (3.0 g, 14.5 mmol) was dissolved in 200 mL MeOH and 6 mL acetic acid. To it was added (1-ethoxycycloproxy)trimethylsilane (8.8 mL, 43.6 mmol), and the mixture was stirred at RT for 2 hours. To it was then added NaBH3CN (5.5 g, 87.3 mmol), and the mixture was sent to 65° C. bath with a condenser attached. The reaction was found cleanly complete in 16 hours. The mixture was concentrated on a rotavap, and EtOAc was poured into the residue. The organic mixture was washed with 1N NaOH and water (×2), dried over MgSO4, concentrated on rotavap and subjected to silica flash column using 0 to 4% MeOH in DCM to isolate 1-cyclopropyl-4-(4-nitrophenyl)piperidine (321) as a thick oil. It was dissolved in 300 mL iPrOH. To it were added 40 μL 6N HCl and 10% Pd/C (1.0 g). The mixture was hydrogenated at 40 psi on a Parr shaker for 16 hours. It was filtered through celite, and the solid cake was thoroughly rinsed with MeOH. The filtrate was concentrated in vacuo to yield 4-(1-cyclopropylpiperidin-4-yl)aniline (322, HCl salt) as a white solid (3.06 g, 83% for two steps).

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