Hydrazine hydrate (1:1) → 6-Bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one

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Reaction Steps

To a mixture of (R)-2-(6-bromo-3-thioxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (75.2 g, 219 mmol) in EtOH (800 mL) was added hydrazine hydrate (98%, 21.9 g, 438 mmol) and the mixture was stirred at ambient temperature overnight. The precipitate was collected by filtration and washed with cold EtOH (3×80 mL) to give 6-bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (6 g, 9%) as a yellow solid. The filtrate was concentrated to give 70 g of crude product, which was purified by chromatography on silica gel (eluting with 10-25% EtOAc in petroleum ether) to give a second batch of (R)-6-bromo-4-methyl-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one (45.9 g, 71%) as a yellow solid. 1H NMR (400 MHz, CDCl3): δ 8.53 (brs, 1H), 7.10 (d, J=8.4 Hz, 1H), 7.03 (s, 1H), 6.89 (d, J=8.4 Hz, 1H), 4.69-4.52 (m, 3H), 1.52 (d, J=6.8 Hz, 3H). SFC (Table 1, Method 32) Rt=6.075 min.; [α]D20=−314.92 (C=0.002 g/mL in methanol).

Provenance & Evidence