反应详情

To a stirred solution of (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-hydroxyphenyl)-2,6-dimethylpyridin-3-yl)acetate (0.04 g, 0.085 mmol), 3-(4-fluorophenyl)propan-1-ol (0.066 g, 0.427 mmol) and Ph3P (0.067 g, 0.256 mmol) in THF (5 mL) was added DEAD (0.041 ml, 0.256 mmol) at 0° C. After 1 h, cold bath was removed and stirred overnight (13 h) at rt. LCMS at this point showed presence of about 50% unreacted phenol. So, added additional 3-(4-fluorophenyl)propan-1-ol (0.066 g, 0.427 mmol), Ph3P (0.067 g, 0.256 mmol) and DEAD (0.041 ml, 0.256 mmol) at r. After stirring for 5 h, reaction mixture was concentrated and purified by prep-HPLC to afford (S)-ethyl 2-(tert-butoxy)-2-(4-(4,4-dimethylpiperidin-1-yl)-5-(4-(3-(4-fluorophenyl)propoxy)phenyl)-2,6-dimethylpyridin-3-yl)acetate (0.0351 g, 0.058 mmol, 68.0% yield) as glassy solid. 1H NMR (500 MHz, CDCl3) δ 7.14-7.23 (m, 3H), 7.06-7.09 (m, 1H), 6.95-7.03 (m, 4H), 6.09 (s, 1H), 4.27 (qd, J=7.1, 10.8 Hz, 1H), 4.18 (qd, J=7.1, 10.7 Hz, 1H), 3.99-4.07 (m, 2H), 3.19 (d, J=12.0 Hz, 1H), 2.88 (t, J=12.3 Hz, 1H), 2.82-2.91 (t, J=7.6 Hz, 2H), 2.61 (s, 3H), 2.28 (d, J=12.0 Hz, 1H), 2.21 (s, 3H), 2.11-2.18 (m, 2H), 2.06 (t, J=11.5 Hz, 1H), 1.56 (dt, J=3.9, 12.6 Hz, 1H), 1.38 (dt, J=3.6, 12.7 Hz, 1H), 1.26 (t, J=7.1 Hz, 3H), 1.21 (s, 9H), 1.18-1.21 (m, 1H), 1.08 (d, J=12.1 Hz, 1H), 0.91 (s, 3H), 0.66 (s, 3H). LCMS (M+H)=605.3.

1. customcold bath was removed
2. stirringAfter stirring for 5 h
3. customreaction mixture
4. concentrationwas concentrated
5. custompurified by prep-HPLC