Acetic Acid → 5-methoxy-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-methoxy-3-formyl-2H-chromene-2-carboxylic acid ethyl ester (1.3 g, 4.96 mmol) in methanol (20 mL) containing molecular sieves (0.7 g) was added commercially available (S)-2-amino-3-cyclohexyl-propionic acid methyl ester (1.2 g, 5.45 mmol) and N,N′-diisopropylethylamine (1.71 mL, 9.91 mmol). The mixture was stirred at 25° C. for 10 hours. At this time, sodium cyanoborohydride (0.62 g, 9.91 mmol) and acetic acid (0.47 mL, 7.49 mmol) were added simultaneously to the reaction mixture, and the reaction mixture was stirred for additional 16 hours at 25° C. The reaction mixture was then filtered through celite and washed with methanol. The filtrate was concentrated in vacuo. Flash column chromatography (eluant-ethyl acetate:petroleum ether 1:19, Rf=0.6) over neutral alumina afforded 5-methoxy-3-[((S)-2-cyclohexyl-1-methoxycarbonyl-ethylamino)-methyl]-2H-chromene-2-carboxylic acid ethyl ester (1.0 g, 45.5%) as an oil.

Provenance & Evidence