Triphenylphosphine → US10188653, Example 17

Participants

Reaction Conditions

Reaction Steps

A solution of triphenylphosphine (65 mg, 0.25 mmol) in THF (1 mL) and a solution of bis(2-methoxyethyl) (E)-diazene-1,2-dicarboxylate (56 mg, 0.24 mmol) in THF (1 mL) were added sequentially to a solution of 3-ethoxy-4-hydroxybenzonitrile (26 mg, 0.16 mmol) and (S)—N-ethyl-2-(3-hydroxypiperidin-1-yl)pyrimidine-5-carboxamide (40 mg, 0.16 mmol) in THF (2 mL) at 20-25° C. The reaction mixture was stirred at 20-25° C. for 16 hours. The mixture was diluted with ether (30 mL), and was washed sequentially with aqueous 1N NaOH solution (1 mL) and brine (1 mL). The organic phase was dried over MgSO4, filtered, and concentrated to provide a crude residue, which was purified via preparative HPLC to afford (R)-2-(3-(4-cyano-2-ethoxyphenoxy)piperidin-1-yl)-N-ethylpyrimidine-5-carboxamide. HPLC: Waters XBridge dC18 4.6×50 mm, 5 μm, 95% water/5% acetonitrile linear to 5% water/95% acetonitrile over 4.0 min, 0.03% NH4OH modifier, 2 mL/min; retention time 2.60 min. MS (ES+) 396.1 (M+H).

Provenance & Evidence