Toluene → Diethyl {[1-(tert-butoxycarbonyl)piperidin-4-yl]methyl}propanedioate

Participants

Reaction Conditions

Reaction Steps

A mixture of 645 mg (2.0 mmol) of 1-(t-butoxycarbonyl)-4-(iodomethyl)piperidine (from EXAMPLE 32, Step A), 660 mg (2.5 mmol) of 18-crown-6, 550 mg (4.0 mmol) of potassium carbonate and 0.60 mL of diethylmalonate in 12 mL of toluene was heated at 80° C. for 20h. The mixture was cooled, partitioned between 75 mL of ether and 50 mL of H2O and the layers were separated. The organic layer was washed with 50 mL of 5% Na2S2O3, 50 mL of sat'd NaCl, dried over MgSO4 and concentrated. Flash chromatography on 30 g of silica gel using 4:1 v/v hexanes/EtOAc, then 2:1 v/v hexanes/EtOAc as the eluant afforded 630 mg (89%) of the title compound: 1H NMR (500 MHz) δ 1.07-1.14 (m, 21), 1.24-1.28 (m, 6H), 1.38-1.45 (m, 1H), 1.45 (s, 9H), 1.66 (d, J=13.0, 2H), 1.83-1.87 (m, 2H), 2.65 (t, J=7.5,22H), 3.41-3.45 (m, 1H), 4.07 (app d, J=12.5,22H), 4.194.22 (m, 2H).

Provenance & Evidence