(a). 2-Acetyl-1-indanone (Liebigs Ann. Chem. 1906, 347, 112) is alkylated
with ethylbromide in acetone in the presence of sodium carbonate to 2-acetyl-
2-ethyl-1-indanone. The acetyl group is brominated with bromine in methanol
and to imidazole by heating in formamide as before. The melting point of the
4(5)-(2,3-dihydro-2-ethyl-1-oxo-1H-inden-2-yl)imidazole is 126-127°C (from
ethyl acetate).
(b). The carbonyl group of 4(5)-(2,3-dihydro-2-ethyl-1-oxo-1H-inden-2-
yl)imidazole is reduced to the alcohol group with sodium borohydride in
ethanol. The product is the mixture of cis-trans stereoisomers, the purification
of which is accomplished by liquid chromatography: cis-isomer as
hydrochloride (melting point 184-185°C), 1H NMR (80 MHz, MeOH-d4): 0.73
(3H, t), 1.86 (2H, m), 3.36 (2H, m), 3.61 (3H, s), 5.15 (1H, s), 7.06 (1H, d),
7.2-7.4 (4H, m), 8.69 (1H, d), and trans-isomer as hydrochloride, 1H NMR
(80 MHz, MeOH-d4): 0.80 (3H, t), 1.84 (2H, m), 3.15 (2H, m), 3.24 (3H, s),
5.15 (1H, s), 6.87 (1H, d), 7.2-7.4 (4H, m), 8.54 (1H, d).
The oxo derivative prepared in step (a) or the hydroxy derivative prepared in
step (b) is hydrogenated in 2 N hydrochloric acid in the presence of 10%
palladium on carbon at 70°C. When the uptake of hydrogen ceases, the
reaction mixture is filtered and made alkaline. The product is extracted with
methylene chloride which is washed with water, dried and evaporated to
dryness. From the residue, which is the product as base, is made the
hydrochloride of 4(5)-(2,3-dihydro-2-ethyl-1H-inden-2-yl)imidazole using dry
hydrogen chloride in ethyl acetate. It has melting point 211-215°C.
