CC(C)([O-])C.[Na+].Br[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([O:15][CH3:16])[CH:9]=1.[NH:17]1[CH2:22][CH2:21][CH:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]1>C1(C)C=CC=CC=1.CC(O)=O.CC(P(C(C)(C)C)C1C(C2[C-]=CC=CC=2)=CC=CC=1)(C)C.[Pd]>[Cl:14][C:11]1[CH:12]=[CH:13][C:8]([N:17]2[CH2:22][CH2:21][CH:20]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH2:19][CH2:18]2)=[CH:9][C:10]=1[O:15][CH3:16]
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 nitrogen and the mixture heated at 80° C. After 45 minutes, the mixture 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. The crude product was purified by flash chromatography using a 12 g silica gel cartridge and gradient elution from 20:1 Hex/EtOAc to 10:1 Hex/EtOAc. 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. The colorless oil was treated with 4.0 M HCl/dioxane (2 mL) and the resulting suspension was diluted with Et2O (4 mL) and stirred at RT for 10 min. The hydrochloride product was collected by filtration, washed with Et2O and dried in vacuo to give ethyl 1-(4-chloro-3-methoxyphenyl)piperidine-4-carboxylate, hydrochloride salt as a white solid (383 mg).
불러오는 중…
