Tetrahydrofuran → HCID 11002155, compound

Participants

Reaction Conditions

Reaction Steps

A stirred suspension of N,N'-carbonyldiimidazole (3.24 g, 20 mmol) in The (40 mL) was warmed up to 50° C., and a solution of 1-benzyl-4-hydroxypiperidine (3.82 g, 20 mmol) in THF (17 mL) was added dropwise over 10 min. Stirring was continued for 2 hrs. at room temperature (RT), and a solution of 6-aminohexanol (3.50 g, 30 mmol) and triethylamine (3.04 g, 30 mmol) in THF (40 mL) was added dropwise over 10 min. When the reaction mixture turned cloudy, the rate of stirring was increased, and a clear solution was obtained within 20-30 min. The mixture was refluxed for 2 hrs., concentrated in vacuo, and the residue was partitioned between ether (70 mL) and water (35 mL). An alternative partitioning between ethyl acetate and water was equally effective. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and evaporated to give the title compound (6.68 g, yield 100%) as a light, yellowish oil. TLC (chloroform-5% methanol) showed a single spot at Rf 0.5; 1H NMR (300 MHz, CDCl3) δ1.37 (m, 4H, CH2), 1.47-1.61 (m, 4H, CH2), 1.67 (m, 2H, CH2, piperidine ring axial protons), 1.88 (m, 2H, CH2, piperidine ring equatorial protons), 2.22 (t, J=9 Hz, 2H, CH--N--CH, piperidine ring axial protons), 2.69 (m, 2H, CH--N--CH, piperidine ring eq. protons), 3.16 (q, J=6.5 Hz, 2H, CH2 --NH), 3.49 (s, 2H, CH2 --Ph), 3.62 (t, J=6.5 Hz, 2H, CH2 --O), 4.66 (m, 1H, CH--O), 4.73 (t, J=6 Hz, 1H, NH), 7.23-733 (m, 5H, Ar--H).

Provenance & Evidence