Potassium Iodide → HCID 2057368, compound

Participants

Reaction Conditions

Reaction Steps

Mix 3-phenoxypropyl bromide (801.5 g, 3.73 mol), potassium iodide (61.8 g, 0.37 mol, 0.10 equivalents) and water (4.0 L) in a 12-L, 3-necked flask fitted with: a stirrer, thermometer in a side-arm adapter, connected to a Firestone® valve and an addition funnel fitted with a gas outlet adapter, connected to a bubbler. Add piperidine (634.6 g, 7.45 mol, 2.0 equivalents) over 1 hour, without cooling under nitrogen. The temperature at the end of the addition is 40° C. Heat the reaction mixture and maintain the temperature at 50° C. for 6 hours. Monitor the progress of the reaction by HPLC (Column=300×3.9 mm Phenomenex Bondclone 10 CN; mobile phase=65% acetonitrile:35% 0.1N ammonium formate buffer; flow=1.5 mL/minute; wavelength=215 nm; RT: 3-phenoxypropyl bromide=2.3 minutes; 37=4.4 minutes). Typically, the conversion is 94%. Cool the reaction mixture to ambient temperature over a time period of 14 hours and extract with dichloromethane (2×4.0 L). Combine the organic extracts and dry over MgSO4 (400 g). Filter off the drying agent and wash with dichloromethane (1.0 L). Concentrate the filtrate (35-40° C./50 torr) to give 800 g, 98% Yield) of 4, as an oil. HPLC analysis shows that 37 is 90% pure. Purify 4 (16.5 g portion) by distillation under vacuum and collect the title compound (10 g) as a colorless liquid at 99-105° C./0.3 mm: 1H NMR (CDCl3, 200 MHz) δ 1.38-1.5 (m, 2H), 1.5-1.64 (m, 4H), 1.9-2.1 (m, 6H), 4.0 (t, 2H), 6.85-6.95 (m. 3H), 7.22-7.3 (t, 2H). Analysis calculated for C14H21NO: C, 76.67; H, 9.65; 6.39. Found: C, 76.55; H, 9.50; N, 6.22. [M+H]+=220 m/e.

Provenance & Evidence