Water → (R)-2-(6-nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester

To a 0° C. suspension of 6-nitro-4H-benzo[1,4]oxazin-3-one (Preparation #2, Step A, 55 g, 283 mmol) in THF (1.1 L) was added drop-wise KHMDS (1M solution in THF, 283 mL, 283 mmol) and the reaction mixture was stirred for 30 min. (S)-2-trifluoromethanesulfonyloxy-propionic acid ethyl ester (Preparation #10, Step B, 142 g, 567 mmol) was added drop-wise and the reaction mixture was stirred for 30 min. Water (1 L) was added and the aqueous solution was extracted with EtOAc (3×1 L). The combined organic phase was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated to give a residue, which was purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether) to give (R)-2-(6-nitro-3-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl)-propionic acid ethyl ester (80.0 g, 96%) as an oil. 1H NMR (CDCl3, 400 MHz): δ 7.96 (dd, J=2.4, 8.8 Hz, 1H), 7.76 (d, J=2.4 Hz, 1H), 7.12 (d, J=8.8 Hz, 1H), 5.34 (q, J=7.2 Hz, 1H), 4.81-4.66 (m, 2H), 4.29 (q, J=7.2 Hz, 2H), 1.68 (d, J=7.2 Hz, 3H), 1.25 (t, J=7.2 Hz, 3H). SFC (Table 2, Method 3) Rt=5.39 min.

1. additionwas added drop-wise
2. extractionthe aqueous solution was extracted with EtOAc (3×1 L)
3. dry with materialThe combined organic phase was dried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationThe filtrate was concentrated
6. customto give a residue, which
7. customwas purified by column chromatography on silica gel (eluting with 10% EtOAc in petroleum ether)

ORD record

ord-e132b4fa068d4141889d9b8e92964089

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115151B2