Acetic Acid → HCID 18697763, compound

Participants

Reaction Steps

To a solution of diisopropylamine (6.1 ml, 43.5 mmol) in tetrahydrofuran (60 ml) was added, at -78° C. under an argon atmosphere, a 1.5 N butyllithium hexane solution (27.4 ml, 41.1 mmol). The mixture was stirred for 30 min. A solution of ethyl propiolate (3.4 ml, 33.5 mmol) in tetrahydrofuran (10 ml) and a solution of 5-methoxymethoxy-4-methyl-2-nitrobenzaldehyde (5.45 g, 24.2 mmol) in tetrahydrofuran (50 ml) were added to the reaction mixture in that order, and the mixture was stirred at -78° C. for additional 1.5 hr. A solution of acetic acid (4.2 ml, 73.3 mmol) in tetrahydrofuran (10 ml) was then added to the reaction mixture, water was then added thereto, and the organic solvent was removed under reduced pressure. The residue was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, a saturated aqueous sodium bicarbonate solution, and saturated brine in that order. It was then dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give ethyl 4-hydroxy-4-(5-methoxymethoxy-4-methyl-2-nitrophenyl)-2-butynoate as a brown oil. Ethyl 4-hydroxy-4-(5-methoxymethoxy-4-methyl-2-nitrophenyl)-2-butynoate was dissolved in toluene (30 ml), 4-methoxybenzylazide (11.8 g, 72.3 mmol) was added to the solution, and the mixture was stirred at 100° C. overnight. The reaction mixture was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (hexane:ethyl acetate=3:2) to give a 1:1 mixture of ethyl 4-(hydroxy-(5-methoxymethoxy-4-methyl-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-5-carboxylate (a-1: low polar product (LP)) and ethyl 5-(hydroxy-(5-methoxymethoxy-4-methyl-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-4-carboxylate (a-2: high polar product (MP)) as a brown crystal (7.57 g, 64%).

Provenance & Evidence