Synthesized (20) using the similar (not exactly same) procedure (Scheme 2) as was written in the paper.
1,4-Diaminobutane was firstly protected by mesitly chloride in DCM (overnight under reflux condition). The protected intermediate was then mono-alkylated with tosylated 3,3-diphenylpropanol under the prescence of sodium hydride (1 equiv.) in DMF. Column purification to seperate di-, mono- substitituded and unreacted starting material. Later 2-bromopropylpthalimide (1.1 equiv.) was alkylated with mono-substituted intermediate to yield compound (33b) as shown in Scheme 2. (33b) was then reduced to primary amine (34b) by hydrazine (10 equiv.) in methonal with overnight stir under r.t.. (34b) was coupled with acyl chloride (28b, 1.1 equiv.) to generated (35c), whose ester bond was later cleaved (36c) by the presence of lithium hydroxide (10 equiv.) in THE/H2O overnight at r.t..
Ethyl chlorformate (1.1 equiv.) and triethylamine (1.1 equiv.) were added to the solution of (36c) (1 equiv.) in THF, and the mixture was cooled to 0 °C. The reaction was allowed to stir for 20 min, after which time it was filtered and added to freshly prepared 1.76 M hydroxylamine (2 equiv.) in methanol. The reaction was stirred at room temperature for 30 min, filtered and concentrated in vacuo to yield the crude (37c). Purification on silica gel (ethyl acetate:methanol 4:2) then afforded pure compound (37c).
Phenol (50 equiv.) was dissolved in 30%HBr in acetic acid and to this mixture was added a solution of (37c) (1 equiv.) in ethyl acetate in three portions over a period of 3 h. After the addition was complete, the reaction mixture was stirred overnight at r.t.. After work up, the crude product was washed with methanol and filtered to yield the hydrobromide salt of compound (20).
Yields for each step vary from ~40% to almost 100%. The total yield was between 10-20%.