Acetic Acid → HCID 18697784, compound

Participants

Reaction Steps

To a solution of diisopropylamine (6.8 ml, 49.0 mol) in tetrahydrofuran (80 ml) was added, at -78° C. under an argon atmosphere, a 1.5 N butyllithium (30.7 ml, 46.0 mmol). The mixture was stirred for one hr. Ethyl propiolate (3.9 ml, 38.4 mmol) and a solution of 4,5-methylenedioxy-2-nitrobenzaldehyde (5.0 g, 25.6 mmol) in tetrahydrofuran (50 ml) were added in that order to the reaction mixture, and the mixture was stirred at -78° C. for additional 1.5 hr. A solution of acetic acid (8.0 ml, 139 mmol) in tetrahydrofuran (20 ml) was then added to the reaction mixture, water was then added thereto, followed by extraction with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, water, 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-(4,5-methylenedioxy-2-nitrophenyl)-2-butynoate as an oil (8.93 g). Ethyl 4-hydroxy-4-(4,5-methylenedioxy-2-nitrophenyl)-2-butynoate thus prepared was dissolved in toluene (75 ml), 4-methoxybenzylazide (14.9 g, 91.1 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=1:2) to give a 1:1 mixture of ethyl 4-(1-hydroxy-(4,5-methylenedioxy-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-5-carboxylate (a-1: low polar product (LP)) and ethyl 5-(1-hydroxy-(4,5-methylenedioxy-2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1,2,3-triazole-4-carboxylate (a-2: high polar product (MP)) (6.42 g, 55%).

Provenance & Evidence