Acetic Acid → HCID 18697763, compound

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%).

1. stirringthe mixture was stirred at -78° C. for additional 1.5 hr
2. additionwas then added
3. customthe organic solvent was removed under reduced pressure
4. extractionThe residue was extracted with ethyl acetate
5. washThe organic layer was washed with dilute hydrochloric acid
6. dry with materialIt was then dried over anhydrous magnesium sulfate
7. customThe solvent was removed under reduced pressure

ORD record

ord-ea01ed900ca54912bedf6b46e846a295

Source dataset

uspto-grants-2000_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06093714