Diisopropylethylamine → Ethyl 2-[(3S)-7-bromo-4-(3-oxo-4H-1,4-benzoxazine-6-carbonyl)-2,3-dihydro-1,4-benzoxazin-3-yl]acetate

Participants

Reaction Conditions

Reaction Steps

DIPEA (46.4 g, 360 mmol) was added to ethyl [(3S)-7-bromo-3,4-dihydro-2H-1,4-benzoxazin-3-yl]acetate (Intermediate 27a, 36 g, 120 mmol), 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carboxylic acid (28 g, 144 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% solution in EtOAc) (152.6 g, 240 mmol) in butyl acetate (100 mL) at rt. The resulting suspension was stirred at 140° C. for 2 hours. The reaction mixture was diluted with EtOAc (700 mL) and washed with saturated NaHCO3 (500 mL), 1 M HCl (500 mL) and brine (500 mL). The organic layer was dried over anhydrous Na2SO4, filtered and evaporated to afford crude product. The residue was purified by a silica chromatography, eluent gradient from 5% to 20% of EtOAc in PE. The pure fraction was evaporated to dryness to afford title compound (33 g, 58%) as an off-white solid.

Provenance & Evidence