Acetic Acid → Ethyl 4-hydroxy-4-(4,5-dimethoxy-2-nitrophenyl)-2-butynoate

Participants

Reaction Steps

1.5N butyllithium (26.8 ml, 40.2 mmole) was added under the argon atmosphere to a solution of diisopropylamine (6.0 ml, 42.8 mmole) in tetrahydrofuran (75 ml) at -78° C., and the mixture was stirred for 1 hour. Next, ethyl propiolate (3.4 ml, 33.5 mmole) and a solution of 4,5-dimethoxy-2-nitrobenzaldehyde (5.0 g, 23.7 mmole) in tetrahydrofuran (50 ml) were added in this sequence, and the reaction mixture was stirred at -78° C. for further 1.5 hours. After a solution of acetic acid (7.0 ml, 122 mmole) in tetrahydrofuran (20 ml) followed by water were added, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, water, a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous saline in this sequence. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was removed under reduced pressure to give ethyl 4-hydroxy-4(4,5-dimethoxy-2-nitrophenyl)-2-butynoate as an oil (8.59 g). Ethyl 4-hydroxy-4(4,5-dimethoxy-2-nitrophenyl)-2-butynoate thus obtained was dissolved in toluene (80 ml), 4-methoxybenzylazide (11.6 g, 71.1 mmole) was added, and the mixture was stirred under heating at 100° C. overnight. After the reaction mixture was cooled to room temperature, it was purified by silica gel column chromatography (hexane:ethyl acetate=2:1).

Provenance & Evidence