Potassium Iodide → 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamide

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(5-bromo-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionamide (prepared as in Example 6, 5.73 g, 11.8 mmol), potassium iodide (2.2 g, 13.0 mmol), 18-crown-6 (0.62 g, 2.4 mmol), triethylamine (4.2 mL, 29.5 mmol), diphenylpropylphosphine (81 μL, 0.35 mmol), and palladium(II) acetate (80 mg, 0.35 mmol) in anhydrous N,N-dimethylformamide (95 mL) in a pressure tube was stirred under carbon monoxide at 65 psi at 25° C. for 30 min. At this time, the reaction was treated with trihexylsilane (8.42 mL, 23.6 mmol) and was stirred under carbon monoxide at 65 psi at 110° C. for 4 h. The reaction was then allowed to cool to 25° C. and was extracted with ethyl acetate (2×200 mL). The combined organic layers were successively washed with a saturated aqueous sodium bicarbonate solution (3×50 mL) and water (3×50 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 70–230 mesh, 1/9 to 7/3 ethyl acetate/hexanes) afforded racemized 2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-formyl-pyrazin-2-yl)-propionamide (1.53 g, 30%) as a white solid.

Provenance & Evidence