4-Methylmorpholine → HCID 178461819, compound

Participants

Reaction Conditions

Reaction Steps

To a cooled solution (−78° C.) of (2S,3R)-4-(benzyloxy)-2-((tert-butoxycarbonyl)amino)-3-methyl-4-oxobutanoic acid (Preparation 66, 4.10 g, 12.2 mmol) in tetrahydrofuran (50 mL) was added N-methylmorpholine (2.0 mL, 18.23 mmol) followed by isobutyl chloroformate (1.67 mL, 12.8 mmol) and the resulting white suspension stirred at −78° C. for 30 minutes. A solution of 4-(tert-butyl)benzene-1,2-diamine (2.40 g, 14.6 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was allowed to warm up to room temperature and stirred at room temperature for 1 hour. The reaction mixture was concentrated in vacuo. The crude product was dissolved in ethyl acetate (200 mL) and washed with aqueous saturated sodium bicarbonate (3×50 mL), water (2×50 mL). The organic layer was concentrated in vacuo and purified by silica gel column chromatography eluting with a gradient of dichloromethane: EtOAc. The residue was dissolved in methanol (50 mL) and palladium hydroxide was added (20% wt % on carbon, 0.43 g). The reaction mixture was stirred under a hydrogen atmosphere (2 atm) at room temperature for 1 hour. The reaction mixture was filtered through a small pad of Arbocel and concentrated in vacuo. The residue was dissolved in acetic acid (100 mL) and stirred at room temperature for 72 hours. The reaction mixture was concentrated in vacuo. The crude product was purified by reverse phase column chromatography eluting with a gradient of water/MeCN to afford the title compound as off-white solid (3.54 g, 78%).

Provenance & Evidence