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

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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 (25 mg, 0.053 mmol), 2-(2,4,5-trifluorophenyl)ethanol (47.0 mg, 0.267 mmol) and Ph3P-resin (69.7 mg, 0.267 mmol) in THF (2 mL) was added DIAD (0.052 mL, 0.267 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-(4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethyl-5-(4-(2,4,5-trifluorophenethoxy)phenyl)pyridin-3-yl)acetic acid (25.2 mg, 0.042 mmol, 79% yield). 1H NMR (500 MHz, DMSO-d6) δ 7.60-7.46 (m, 2H), 7.21 (d, J=8.4 Hz, 1H), 7.08-6.87 (m, 3H), 5.85 (br. s., 1H), 4.26 (q, J=6.2 Hz, 2H), 3.23 (br. s., 1H), 3.07 (t, J=6.2 Hz, 2H), 2.85-2.73 (m, 1H), 2.43 (s, 3H), 2.16 (br. s., 1H), 2.05 (s, 3H), 1.96-1.86 (m, 1H), 1.48 (br. s., 1H), 1.29 (br. s., 1H), 1.17 (d, J=13.6 Hz, 1H), 1.13 (s, 9H), 1.01 (d, J=12.5 Hz, 1H), 0.84 (br. s., 3H), 0.59 (br. s., 3H). LCMS (M+H)=599.2.

Provenance & Evidence