Acetic Acid → HCID 15035851, compound

Participants

Reaction Steps

A 500-mL, three-necked, round-bottomed flask was equipped with a magnetic stirrer, a heating mantle, a standard condenser with a N2 inlet, a 250-mL addition funnel, and a glass stopper. A mixture of benzylamine (10.71 g, 100 mmol), HCl (37%, 4.93 g, 50 mmol), glacial acetic acid (6.0 g, 100 mmol) and paraformaldehyde (6.31 g, 210 mmol) in CH3OH (100 mL) was brought to gentle reflux with stirring under N2 over 15 min. A solution of 1-benzyl-4-piperidinone (43, 18.93 g, 100 mmol) and glacial acetic acid (6.01 g, 100 mmol) in CH3OH (100 mL) was then added dropwise over 1 h and this was followed by a period of reflux for an additional 18 h. Upon cooling the mixture to RT, the solvent was removed and the resulting red oil was redissolved in H2O (100 mL). Combined extracts (ether, 2×100 mL) of the acidic aqueous layer were discarded. Basification of the chilled (10° C., ice water bath) water layer to pH~12 was affected by the addition of 10% NaOH. Combined extracts (ether, 4×60 mL) were dried (Na2SO4, 1 h), filtered, and concentrated to give a viscous red oil. This oil was digested (Skelly B, 2×250 mL, 20 min), and the supernatant extracts were concentrated and then distilled (190°-215° C./10-5 mm Hg) to give an oil. Crystallization of the oil was induced by dissolving the oil in hot pentane (800 mL) and then chilling (-10° C.) the solution to give 14.66 g (45.8%) of white, crystalline ketone (19); mp 82.5°-83.5° C. Concentration (hot plate) of the mother liquor to ~80 mL produced a second crop (0.81 g, 2.5%) of 3,7-dibenzyl-3,7-diazabicylco[3.3.1]nonan-9-one (19); mp 81.5°-82.0° C. The total yield was (15.47 g, 48.3%).

Provenance & Evidence