反应详情

Anhydrous potassium carbonate (0.40 g, 2.9 mmol) was added to a stirred solution of compound (6-fluoro-4-trifluoromethanesulfonyloxy-naphthalen-2-yl)-acetic acid methyl ester (which may be prepared as described above; 0.37 g, 1 mmol) and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.30 g, 0.97 mmol) in dry DMF-MeOH (4:1, 5 mL) in a pressure tube. The mixture was deoxygenated by bubbling with argon for 15 min. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (available from Sigma-Aldrich; 80 mg, 0.1 mmol) was added under argon. The mixture was heated at reflux for 12 h and then cooled. Ethyl acetate (20 mL) was added and the mixture was filtered through a pad of celite. The celite was washed with ethyl acetate and the combined filtrates were concentrated under reduced pressure. The residue was purified by silica gel column chromatography (100-200 mesh), using 5% ethyl acetate/hexanes as eluent, to give 4-(7-fluoro-3-methoxycarbonylmethyl-naphthalen-1-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.21 g, 54%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 7.78 (dd, J=6.6, 4.4 Hz, 1H), 7.64 (s, 1H), 7.51 (dd, J=7.1, 1.1 Hz, 1H), 7.21-7.26 (m, 2H), 5.77 (s, 1H), 4.12 (s, 2H), 3.70-3.76 (m, 7H), 2.45-2.50 (m, 2H), 1.52 (m, 9H); MS cald. for C23H27FNO4 [(M+H)+] 400, obsd. 400.2.

1. customThe mixture was deoxygenated
2. additionwas added under argon
3. temperatureThe mixture was heated
4. temperatureat reflux for 12 h
5. temperaturecooled
6. filtrationthe mixture was filtered through a pad of celite
7. washThe celite was washed with ethyl acetate
8. concentrationthe combined filtrates were concentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (100-200 mesh)