反应详情

A mixture of methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(2,2,2-trifluoroacetyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (intermediate 4) (0.250 g, 0.464 mmol) and K2CO3 (0.064 g, 0.464 mmol) in MeOH was stirred at room temperature for 24 h. The reaction was diluted with Et2O (50 mL), washed with water (10 mL), brine (10 mL), dried (Na2SO4), filtered and concentrated to give a pale yellow residue which was purified by reverse phase preparative-HPLC, eluting with MeCN/H2O, to afford methyl 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetate (0.117 g, 57% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.28-7.32 (1H, m), 7.15-7.20 (1H, m), 7.13 (2H, d, J=6.7 Hz), 4.79 (1H, s), 3.75 (1H, d, J=16.2 Hz), 3.69 (3H, s), 3.48 (1H, quin, J=6.6 Hz), 3.42 (1H, d, J=16.5Hz), 2.94-3.05 (2H, m), 2.17 (1H, br. s.), 1.39 (6H, s), 1.26 (3H, d, J=6.4 Hz), 1.09 (3H, d, J=6.7 Hz), 0.95 (9H, s). LCMS (M+H) calcd for C26H36FN2O3: 443.2. found: 433.3.

1. washwashed with water (10 mL), brine (10 mL)
2. dry with materialdried (Na2SO4)
3. filtrationfiltered
4. concentrationconcentrated
5. customto give a pale yellow residue which
6. customwas purified by reverse phase preparative-HPLC
7. washeluting with MeCN/H2O