Example 84 Steps for the synthesis of ethyl 3-[4-(5-hydroxy-2-methylphenoxy)-2-methylphenyl]-propionate:
Step A Preparation of 5-methoxy-2-methylphenol
A solution of 2-hydroxy-4-methoxybenzaldehyde (5.00 g, 32.86 mmol), carbon-loaded palladium (10%, 3.50 g, 3.28 mmol) in ethanol (32 mL), and acetic acid (3 mL) was placed in a reactor and the reaction mixture was stirred at 60 psi hydrogen pressure. After overnight reaction, the mixture was filtered through a diatomaceous earth pad and washed with methanol. The filtrate was concentrated under reduced pressure and the resulting crude product was purified by fast column chromatography with hexane:ethyl acetate (2:1) as eluent to give 5-methoxy-2-methylphenol (3.96 g, 87% yield). Thin layer chromatography (TLC) Rf = 0.58 (unfolding agent: hexane:ethyl acetate 2:1).1H NMR (300MHz, CDCl3) δ: 2.18 (s, 3H), 3.75 (s, 3H), 6.42 (m, 2H), 7.00 (d, 1H, J = 8.9Hz).
