Diisopropylamine → Ethyl 8-nitro-4-oxo-2-(3-(trifluoromethyl)phenyl)-1,4-dihydroquinoline-3-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (7.00 mL, 50.0 mmol) in THF (100 mL) was cooled to −78° C., and n-BuLi (20.0 mL, 2.5 M in hexanes, 50.0 mmol) was added. After stirring for 20 min at −78° C., ethyl acetate (5.72 mL, 58.6 mmol) was added. The solution was stirred at −78° C. for 10 min, warmed to 0° C. and stirred for 10 min, then cooled back to −78° C. A solution of 8-nitro-2-(3-(trifluoromethyl)phenyl)-4H-benzo[d][1,3]oxazin-4-one 3 (9.85 g, 29.3 mmol) in THF (100 mL) was added over 5 min to the LDA/EtOAc mixture. The reaction was stirred at −78° C. for 1 h, then warmed to room temperature over 2 h. 1N NaOH (50 mL) was then added, and the reaction stirred vigorously overnight. Brine (50 mL) was added, and the organic layer separated. The aqueous layer was extracted with ethyl acetate (2×100 mL), and the combined organic layers dried with MgSO4 and concentrated under reduced pressure. The remaining material was purified by MPLC (using a gradient of 20% to 50% EtOAc in pentane) to give 36 (5.00 g, 42% yield).

Provenance & Evidence