Triphenylphosphine → (2S)-2-tert-butoxy-2-[5-[4-[(2-chlorothiazol-5-yl)methoxy]phenyl]-4-(4,4-dimethyl-1-piperidyl)-2,6-dimethyl-3-pyridyl]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 (25 mg, 0.053 mmol), (2-chlorothiazol-5-yl)methanol (23.94 mg, 0.160 mmol) and Ph3P-resin (69.7 mg, 0.267 mmol) in THF (2 mL) was added DEAD (0.025 mL, 0.160 mmol) at rt. After 18 h, mixture was filtered to remove polymer, concentrated and treated with 1N NaOH (1.067 mL, 1.067 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-((2-chlorothiazol-5-yl)methoxy)phenyl)-4-(4,4-dimethylpiperidin-1-yl)-2,6-dimethylpyridin-3-yl)acetic acid (0.9 mg, 1.573 μmol, 2.95% yield). 1H NMR (400 MHz, METHANOL-d4) δ 7.69 (s, 1H), 7.37-7.32 (m, 1H), 7.24-7.17 (m, 2H), 7.16-7.10 (m, 1H), 5.55 (s, 1H), 5.42 (s, 2H), 2.68 (s, 3H), 2.28 (s, 3H), 1.36 (br. s., 3H), 1.31 (br. s., 1H), 1.20 (s, 9H), 0.84 (s, 6H). 4H of piperidine were not resolved. LCMS (M+H)=572.5.

Provenance & Evidence