1,2-Dimethoxyethane → (R)-2-[3-(6-Chloro-pyridin-3-yl)-benzyl]-morpholine-4-carboxylic Acid Tert-butyl Ester

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Reaction Steps

To the solution of 0.30 g (0.84 mmol) (R)-2-(3-bromo-benzyl)-morpholine-4-carboxylic acid tert-butyl ester (example 97, intermediate (d)) in 12 mL 1,2-dimethoxyethane 97 mg (84 μmol) tetrakis(triphenylphosphine)palladium(0) were added. After 30 min. 0.48 g (3.0 mmol) 2-chloropyridine-5-boronic acid and 0.22 g (2.1 mmol) sodium bicarbonate dissolved in 6 mL water were added successively and the reaction stirred for 2.5 h under reflux. After cooling down to room temperature the reaction mixture was poured on saturated aqueous potassium carbonate solution and extracted three times with ethyl acetate. The organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography using MPLC on silica gel with ethyl acetate: n-heptane (1:1) as eluant to give the compound as colorless oil (35%).

Provenance & Evidence