Triphenylphosphine → (S)-2-(tert-butoxy)-2-(5-(4-(3,4-difluorophenethoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid

Participants

Reaction Steps

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 (20 mg, 0.043 mmol), 2-(3,4-difluorophenyl)ethanol (33.7 mg, 0.213 mmol) and Ph3P-resin (33.5 mg, 0.128 mmol) in THF (2 mL) was added DEAD (0.020 mL, 0.128 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (0.854 mL, 0.854 mmol) in MeOH (1 mL) at 75° C. for 16 h. Mixture was then cooled and purified by prep-HPLC to afford (S)-2-(tert-butoxy)-2-(5-(4-(3,4-difluorophenethoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid (1.7 mg, 2.93 μmol, 6.86% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.48-7.39 (m, 1H), 7.39-7.32 (m, 1H), 7.24-7.14 (m, 2H), 7.07-6.99 (m, 3H), 5.86 (s, 1H), 4.34-4.18 (m, 2H), 3.24 (br. s., 1H), 3.07 (t, J=6.4 Hz, 2H), 2.85-2.76 (m, 1H), 2.44 (s, 3H), 2.18 (d, J=10.3 Hz, 1H), 2.05 (s, 3H), 1.98-1.90 (m, 1H), 1.49 (br. s., 1H), 1.36-1.23 (m, 1H), 1.18 (d, J=13.2 Hz, 1H), 1.13 (s, 9H), 1.02 (d, J=13.2 Hz, 1H), 0.85 (s, 3H), 0.60 (s, 3H). LCMS (M+H)=581.5.

Provenance & Evidence