Water → 2-[6-(1-Benzhydryl-3-methyl-azetidin-3-yloxy)-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl]-propionic acid ethyl ester

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Reaction Conditions

Reaction Steps

A mixture of ethyl 2-(6-hydroxy-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (Example #65, Step C, 0.200 g, 0.754 mmol), methanesulfonic acid 1-benzhydryl-3-methyl-azetidin-3-yl ester (0.275 g, 0.829 mmol) and Cs2CO3 (0.491 g, 1.508 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% to 10% EtOAc in petroleum ether) to give 2-[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 (0.300 g, 79%). 1H NMR (CDCl3, 400 MHz): δ 7.44 (m, 4H), 7.30 (m, 3H), 7.29 (m, 1H), 7.28 (m, 2H), 6.87 (d, J=8.8 Hz, 1H), 6.28 (d, J=8.8 Hz, 1H), 6.22 (s, 1H), 5.32 (q, J=7.2 Hz, 1H), 4.55 (d, J=17.6 Hz, 2H), 4.42 (s, 1H), 4.09 (q, J=7.2 Hz, 2H), 3.38 (m, 2H), 3.19 (m, 2H), 1.59 (m, 6H), 1.16 (t, J=7.2 Hz, 3H).

Provenance & Evidence