Acetic Acid → 10-(5-Fluoro-3-pyridyl)-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 1-(5-fluoro-3-pyridyl)-4-[1-(4-isopropoxy-3-methyl-benzoyl)-4-piperidylidene]butane-1,3-dione (100 mg, 0.23 mmol) in acetic acid (1.7 mL, 30 mmol) was heated at 120° C. for 1 h. The reaction mixture was cooled to 25° C. and repartitioned between ethyl acetate and water. The aqueous layer was separated and extracted with ethyl acetate (3×50 mL). The combined organics were washed with brine, dried over magnesium sulfate, and concentrated to dryness. The crude product was purified on silica gel utilizing a gradient of 60-100% ethyl acetate in hexanes to yield 10-(5-fluoro-3-pyridyl)-3-(4-isopropoxy-3-methyl-benzoyl)-11-oxa-3-azaspiro[5.5]undec-9-en-8-one (92 mg). 1H NMR (400 MHz, CDCl3) δ 8.86 (s, 1H), 8.61 (d, J=2.7 Hz, 1H), 7.74 (ddd, J=9.0, 2.7, 1.9 Hz, 1H), 7.28-7.24 (m, 2H), 6.84 (d, J=9.0 Hz, 1H), 6.09 (s, 1H), 4.58 (dt, J=12.1, 6.1 Hz, 1H), 3.42 (br s, 2H), 2.68 (s, 2H), 2.27-2.22 (m, 6H), 1.75 (m, 3H), 1.36 (d, J=6.0 Hz, 6H). ESI-MS m/z calc. 438.20, found 439.3 (M+1)+; Retention time: 1.78 minutes (3 min run).

Provenance & Evidence