Hydrochloric Acid → 8-Benzyl-8-azabicyclo(3.2.1)octan-3-one

Participants

Reaction Conditions

Reaction Steps

Under N2, a solution of benzylamine (36.1 ml, 0.33 mol) in water (435 ml) was added within 45 min at 3 to 8° C. to a solution of 1,4-butane dialdehyde (1.15 equiv.), 1,3-acetone dicarboxylic acid (1.5 equiv.) and sodium acetate trihydrate (2 equiv.) in 330 ml water as described in Example 1, Step (a). The mixture was warmed up to 50° C. over 5 h and kept at this temperature for 2 h. After cooling to 20-25° C., 80 ml conc. HCl was added and the solution was washed with TBME (2×240 ml). The pH of the aqueous phase was adjusted to 7-8 with NaOH and the product layer was separated. The aqueous phase was extracted with TBME (3× with a total of 240 ml). The combined product phases were dried over Na2SO4 and concentrated as completely as possible under vacuum at 50°. Yield: 68.7 g (90% abs.). Assay (HPLC): 93% pure vs. standard.

Provenance & Evidence