Ethyl Propionate → Ethyl 4-hydroxy-4-(2-nitrophenyl)-2-butynoate

Participants

Reaction Steps

To a solution of diisopropylamine (6.6 ml, 47.1 mmole) in tetrahydrofuran (80 ml) at -78° C. under an argon atmosphere was added 2.5 N butyllithium (17.4 ml, 43.5 mmole), and the mixture was stirred for 30 minutes. To this reaction mixture were next added a solution of ethyl propionate (4.0 ml, 39.5 mmole) in tetrahydrofuran (20 ml) and a solution of 2-nitrobenzaldehyde (4.0 g, 26.5 mmole) in tetrahydrofuran (20 ml) in this sequence, and the resulting mixture was further stirred at -78° C. for 30 minutes. To the reaction mixture were added tetrahydrofuran (10 ml) followed by water, and the mixture was extracted with ethyl acetate. The organic layer was washed with dilute hydrochloric acid, 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-(2-nitrophenyl)-2-butynoate as an oily product. After the ethyl 4-hydroxy-4-(2-nitrophenyl)-2-butynoate thus obtained was dissolved in toluene (80 ml), 4-methoxybenzylazide (13.0 g, 79.7 mmole) was added to the solution and stirred under heating at 100° C. for 3 hours. The reaction mixture was then cooled to room temperature. Precipitates were collected by filtration, washed with toluene and desiccated to give ethyl 5-[hydroxy-(2-nitrophenyl)methyl]-1-(4-methoxybenzyl)-1,2, 3-triazole-4-carboxylate (a-2: highly polar product (MP)) (2.55 g, 15.7%). Furthermore, the filtrate was concentrated and purified by silica gel column chromatography (toluene : ethyl acetate =1:1) to give a 3:1 mixture (6.09 g, 37.4%) of ethyl 4-(hydroxy-(2-nitrophenyl)methyl)-1-(4-methoxybenzyl)-1, 2,3-triazole-5-carboxylate (a-1: low polar product (LP)) and a compound a-2.

Provenance & Evidence