Toluene → HCID 89782323, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of Pd(PPh3)4 (18 mg, 0.016 mmol), tributyl(1-ethoxyvinyl)stannane (0.12 mL, 0.34 mmol), (8-bromoquinolin-2-yl)(morpholino)methanone (Example 167a; 100 mg, 0.31 mmol), and toluene (1.5 mL) were stirred in a sealed 5 mL glass microwave tube under argon at 100° C. for 63 h. Formation of both the vinyl ether (M+1=313.1) and the methyl ketone (M+1=285.0) were detected by LCMS. The mixture was concentrated under reduced pressure, and the residue was adsorbed onto silica gel. Chromatographic purification (silica gel, 10-70% EtOAc in hexanes) afforded a mixture of the vinyl ether and the methyl ketone as a colorless oil. The material was dissolved in THF (3 mL), the solution was cooled to 0° C., 2 drops of 1N HCl were added and the solution was stirred at 0° C. for 5 min. EtOAc (25 mL) was added to the reaction mixture and the solution was washed successively with 1N NaOH (5 mL), water (10 mL) and brine (10 mL). The combined aq. washes were extracted with 25% IPA in CHCl3, and all organic layers were then combined, dried over MgSO4, filtered, and concentrated in vacuo to give 1-(2-(morpholine-4-carbonyl)quinolin-8-yl)ethanone (81.4 mg, 0.286 mmol, 92% yield) as a white film: 1H NMR (400 MHz, DMSO-d6) δ ppm 8.62 (d, J=8.6 Hz, 1H), 8.18-8.24 (m, 1H), 7.95 (dd, J=7.1, 1.3 Hz, 1H), 7.72-7.83 (m, 2H), 3.72 (s, 4H), 3.56 (d, J=4.7 Hz, 4H), 2.79 (s, 3H). m/z (ESI, +ve ion) 285.0 (M+H)+.

Provenance & Evidence