Water → HCID 66732089, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of tert-butyl 2-(4-chlorobenzyl)-4-oxopiperidine-1-carboxylate (8.737 g, 26.98 mmol) in DME (200 mL) under nitrogen was added simultaneously 1-(isocyanomethyl-sulfonyl)-4-methylbenzene (7.90 g, 40.47 mmol) in 200 mL DME and potassium tert-butoxide (81 mL, 80.94 mmol) over 1 hour so that the temperature never rose above 0° C. The solution was stirred at −20° C. for 2 h and then let to warm to room temperature overnight. Water (200 mL) was added to the orange reaction mixture and the solution was stirred for 20 min and then extracted with 3× diethyl ether and 3× EtOAc. The organic phases were combined and dried over Na2SO4 and evaporated to give a brown residue. Further purification was done on Biotage (340 g column, 3 runs, heptane/EtOAc, gradient 20-60% EtOAc) to give tert-butyl 2-(4-chlorobenzyl)-4-cyanopiperidine-1-carboxylate (5.54 g, 61%). 1H NMR (400 MHz, cdcl3) δ, 1.21-1.50 (m, 9H), 1.58-2.14 (m, 4H), 2.55-3.27 (m, 4H), 4.06-4.25 (m, 1H), 4.34-4.60 (m, 1H), 7.02-7.34 (m, 4H). MS m/z 235, 237 (M-C5H8O2+H)+

Provenance & Evidence