Water → HCID 86727386, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 2-(7-fluoro-6-hydroxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (0.200 g, 0.706 mmol), methanesulfonic acid 1-benzhydryl-3-methyl-azetidin-3-yl ester (Preparation #3, Step B, 0.257 g, 0.777 mmol) and Cs2CO3 (0.460 g, 1.412 mmol) in DMF (8 mL) was stirred at 90° C. for 3 h. The reaction mixture was cooled to ambient temperature and poured into water (150 mL). The aqueous mixture was extracted with EtOAc (3×20 mL) and the combined organic phase was washed with brine (3×20 mL), dried over anhydrous Na2SO4, filtered and evaporated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 5-10% EtOAc in petroleum ether) to give 2-[7-fluoro-6-(1-benzhydryl-3-methyl-azetidin-3-yloxy)-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl]-propionic acid ethyl ester as a white solid (0.280 g, 76%). 1H NMR (CDCl3, 400 MHz): δ 7.44 (m, 4H), 7.31 (m, 2H), 7.29 (m, 2H), 7.27 (m, 2H), 6.87 (d, J=10.4 Hz, 1H), 6.22 (d, J=7.6 Hz, 1H), 5.45 (q, J=7.2 Hz, 1H), 4.55 (d, J=15.2 Hz, 2H), 4.41 (s, 1H), 3.98 (q, J=7.2 Hz, 2H), 3.34 (d, J=7.6 Hz, 2H), 3.19 (d, J=7.6 Hz, 2H), 1.59 (s, 3H), 1.56 (d, J=7.2 Hz, 3H), 1.16 (t, J=7.2 Hz, 3H).

Provenance & Evidence