4-Methylmorpholine → HCID 178500488, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (2S)-2-[(tert-butoxycarbonyl)amino]-4-methoxy-3-methyl-4-oxobutanoic acid (Preparation 62, 8.45 g, 32.3 mmol) in THF (300 mL) was cooled to −78° C. and NMM (5.3 mL, 48.5 mmol) was added followed by a solution of isobutylchloroformate (4.44 mL, 34 mmol) in THF (20 mL) dropwise over 30 minutes. The resulting solution was added to a solution of 4-tert-butyl-1,2-diaminobenzene (5.95 g, 36.22 mmol) in THF (100 mL) via cannula at −78° C. The reaction was stirred at −78° C. for 1 hour, then allowed to warm to room temperature for 3 hours. The reaction was concentrated in vacuo and diluted with EtOAc (300 mL). The solution was washed with saturated aqueous NaHCO3 solution (2×100 mL), brine (3×100 mL), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in AcOH (150 mL) and stirred at room temperature for 4 days. The reaction was evaporated to dryness azeotroping with dioxane. The residue was purified using reverse phase column chromatography eluting with 5-40% MeCN in 0.1% formic acid in water. The acetonitrile was evaporated and the remaining aqueous solution was basified with saturated aqueous NaHCO3 solution. The product was extracted with EtOAc, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified using silica gel column chromatography eluting with DCM/TBME 9/1 to afford the title compound as a yellow solid (7.25 g, 58%).

Provenance & Evidence