Ethyl 4-piperidinecarboxylate → Ethyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylate

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A 10-mL round bottom flask containing a magnetic stir bar and fitted with a condenser and a inert gas inlet was charged successively with sodium tert-butoxide (304 mg, 3.16 mmol), acetato (2′-di-t-butylphosphino-1,1′-biphenyl-2-yl) palladium (II) (20.90 mg, 0.045 mmol) and a solution of 4-bromo-1-chloro-2-methoxybenzene (500 mg, 2.258 mmol) and ethyl piperidine-4-carboxylate (426 mg, 2.71 mmol) in anhydrous toluene (2.5 mL). The flask was purged with argon and the mixture heated at 80° C. After 45 min, the reaction was cooled to RT, diluted with Et2O (50 mL) and washed with water (2×15 mL) and brine (15 mL). The organic layer was dried (MgSO4) and concentrated on a rotary evaporator to give the crude product, which was purified by flash chromatography using a 12 g silica gel cartridge and 20:1 Hex/EtOAc to 10:1 Hex/EtOAc to elute the product. The fractions containing the product were pooled and concentrated on a rotary evaporator to give ethyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylate (380 mg, 1.276 mmol, 56% yield) as a colorless oil. LC/MS [M+H]+=298.28. 1H-NMR (400 MHz, CDCl3) δ 7.18 (1 H, d, J=8.57 Hz), 6.50 (1 H, s), 6.44 (1 H, s), 4.15 (2H, q, J=7.10 Hz), 3.87 (3 H, s), 3.58 (2 H, dt, J=12.47, 3.65 Hz), 2.79 (2 H, s), 2.38-2.47 (1 H, m), 2.02 (2 H, d, J=11.42 Hz), 1.88 (2 H, s), 1.26 (3 H, t, J=7.14 Hz).

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