Ethyl 1-(2-chloroethyl)piperidine-3-carboxylate → Ethyl 1-azabicyclo[3.2.1]octane-5-carboxylate
Reaction equation
Cl[CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][CH2:7][CH:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:5]1.C(NC(C)C)(C)C.[Li]>O1CCCC1>[N:4]12[CH2:5][C:6]([C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:2][CH2:3]1)[CH2:7][CH2:8][CH2:9]2Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
Ethyl 1-(2-chloroethyl)piperidine-3-carboxylate (3.73 g, 17 mmol) in tetrahydrofuran (30 mL) was cooled to −65° C. under nitrogen; lithium diisopropylamine (17 mL, 2 M in tetrahydrofuran) was added slowly to the solution at −65° C. in 25 min. The mixture was allowed to warm up to room temperature and stirred overnight. The reaction was quenched with potassium carbonate and extracted with ether. The combined organic layer were dried over anhydrous magnesium sulfate, filtered and concentrated. The resulting orange oil was co-evaporated with dichloromethane three times. The extracts were combined and concentrated to give the ethyl 1-azabicyclo[3.2.1]octane-5-carboxylate (1.9 g, yield 61%). 1H-NMR (400 MHz, CD3OD) δ: 1.33 (t, 3H), 1.90-2.25 (m, 5H), 2.32-2.47 (m, 1H), 3.20-3.38 (m, 3H), 3.40-3.53 (m, 1H), 3.57-3.80 (m, 2H), 4.20 (q, 2H). LC-MS (ESI) (m/z): 184 (M+1)+.