Diisopropylethylamine → tert-Butyl (3R)-3-[{[2,2-dimethyl-3-oxo-7-(trifluoromethyl)-4-(2-{[1-(trifluoromethyl)propyl]amino}-ethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl (3R)-3-[{[4-(2-aminoethyl)-2,2-dimethyl-3-oxo-7-(trifluoromethyl)-3,4-dihydro-2H-1,4-benzoxazin-6-yl]carbonyl}(isopropyl)amino]piperidine-1-carboxylate (278 mg) in methylene chloride (2 ml) were added 1,1,1-trifluoro-2-butanone (0.1 ml), diisopropylethylamine (0.34 ml), and titanium tetrachloride (0.05 ml), and the mixture was stirred at room temperature for 3 hours. Then, to the reaction solution were added sodium cyanoborohydride (110 mg) and methanol (10 ml), and the mixture was stirred at room temperature for one hour. To the reaction solution was added a saturated aqueous sodium hydrogen carbonate solution (10 ml), and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=3:1) to give the title compound (100 mg) as amorphous.

Provenance & Evidence