Triethylamine → (E)-methyl 4-(2-(tert-butoxycarbonyl)ethylamino)-4-oxobut-2-enoate

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Reaction Steps

Mono methyl fumarate (1.7 g, 13.1 mmol) was taken up in 20 mL of CH2Cl2 along with oxalyl chloride (1.1 mL, 13.1 mmol). After a few drops of DMF were added, the reaction mixture was stirred at room temperature until all the solids had dissolved and all gas evolution had ceased (1 h). This freshly prepared solution of the acid chloride was added dropwise at 0° C. to a solution containing tert-butyl 2-aminoethylcarbamate (2.1 g, 13.1 mmol) and Et3N (2.8 mL, 19.6 mmol) in 200 mL of CH2Cl2. The resulting reaction mixture was warmed to room temperature and stirred for 2 h. It was then washed with brine, dried (Na2SO4) and concentrated under reduced pressure. Purification by chromatography (CH2Cl2) afforded 2.2 g of (E)-methyl 4-(2-(tert-butoxycarbonyl)ethylamino)-4-oxobut-2-enoate (62% yield). (E)-Methyl 4-(2-(tert-butoxycarbonyl)ethylamino)-4-oxobut-2-enoate (2.2 g, 8.1 mmol) was taken up in 10 mL of 4 M HCl in dioxane. The resulting reaction mixture was allowed to stand at room temperature for 1 h, then diluted with 50 mL of EtOAc and concentrated under reduced pressure to afford the HCl salt of (E)-methyl 4-(2-aminoethylamino)-4-oxobut-2-enoate.

Provenance & Evidence