2,2,2-Trifluoroethanol → 2-acetamido-N-tert-butyl-2-(3-(4-chlorobenzyl)-3-formamidocyclobutyl)hex-5-enamide

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Reaction Steps

A solution of N-(1-(4-chlorobenzyl)-3-pent-4-enoylcyclobutyl)formamide (0.5 g, 1.64 mmol) and ammonium acetate (1.14 g, 9.84 mmol) in 2,2,2-trifluoroethanol (4 mL). was treated with tert-butyl isocyanide (1.1 mL, 9.84 mmol) and stirred at room temperature for 3 days. Once complete, the solution was diluted with ethyl acetate (15 mL) and quenched with 2M HCl (10 mL). After stirring vigorously for 1 h, the phases were separated and the organic layer was washed with water and saturated aqueous sodium chloride, dried over MgSO4, filtered and concentrated. Purification by column chromatography (gradient 25-75% ethyl acetate in heptane) afforded the subject compound as a colorless oil (330, mg, 45% yield). ESI MS found for C24H34ClN3O3 m/z [448.6 (M+1), 470.6 (M+Na+), 446.3 (M−1)].

Provenance & Evidence