Synthesis
A mixture of ethyl p-methoxyphenylacetate (4 g, 20.62 mmol),
paraformaldehyde (1.05 g, 35.0 mmol) and TBAI (0.381 g, 1.03
mmol) was heated in PhMe (16 ml) at 80-85 ºC for 3.5 hours. The
reaction mixture was allowed to cool. Then, a solution of Me2NH in
THF was added to the reaction mixture at 0 ºC in the presence of
catalytic FeCl3 (0.160 g, 0.001 mol) and stirred for 45 minutes. After
completion of the reaction, 100 ml water was added to the reaction mixture and aqueous
layer was acidified with conc. HCl (pH = 2). Aqueous layer was washed with DCM (3x 50
ml) and made alkaline (pH = 8) using 5% NaOH solution, extracted with DCM (3x 50 ml),
washed with water, brine, dried over anhydrous Na2SO4, filtered and concentrated under
reduced pressure. Column chromatographic purification over silca gel (0.5% MeOH in
CHCl3) furnished aminoester 65 as a thick colourless oil (3.08 g). When the reaction was carried out without catalyst, it took 48 hours for
completetion.
