Pyridine → Methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate

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Reaction Steps

A mixture of Cu(OAc)2 (8.21 mg, 0.045 mmol) and pyridine (3.66 μl, 0.045 mmol) in CH2Cl2 (0.5 mL) was stirred for 5 min. Added to this were methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (intermediate 5) (10 mg, 0.023 mmol), phenylboronic acid (5.51 mg, 0.045 mmol) and 17 mg molecular sieves. The resulting mixture was stirred at room temperature open to air for 17 h. The mixture was adsorbed directly onto silica gel and purified by flash chromatography (Biotage; 0%-50% EtOAc/hexane). 1H NMR (500 MHz, CDCl3) δ ppm 7.38 (ddd, J=8.4, 5.8, 2.3 Hz, 1H), 7.27-7.16 (m, 5H), 6.87-6.73 (m, 3H), 4.86 (s, 1H), 3.94 (d, J=15.6 Hz, 1H), 3.73 (s, 3H), 3.69 (d, J=15.6 Hz, 1H), 3.55 (dt, J=13.0, 6.4 Hz, 1H), 3.44-3.34 (m, 1H), 3.28 (d, J=12.5Hz, 1H), 1.49 (d, J=3.7 Hz, 6H), 1.33 (d, J=6.1 Hz, 3H), 1.17 (d, J=6.7 Hz, 3H), 1.01 (s, 9H). 19F NMR (500 MHz, CDCl3) δ ppm −113.64. LCMS (M+H) calcd for C32H40FN2O3: 519.30. found: 519.45.

Provenance & Evidence