Dissolved organic nitrogen solid phase extraction

In a 50-mL Schlenk flask, copper(I) iodide (71 mg, 0.40 mmol, 2.5 mol%) and bis(triphenylphosphine)palladium(II) chloride (263 mg, 0.400 mmol, 2.5 mol%) under nitrogen were dissolved in degassed diisopropylamine (25 mL). To this solution, ethynyltrimethylsilane (1.47 g, 15.0 mmol) and 1-bromonaphthalene (3.11 g, 15.0 mmol) were added and stirred for 4 days at ambient temperature. The solid was filtered and the solvent removed under reduced pressure. The residue was dissolved in sodium bicarbonate solution (100 mL) and dichloromethane (100 mL), the phases separated, and the aqueous phase extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with saturated sodium chloride solution (2 x 50 mL) and dried over MgS04. Then, the solvent was removed in vacuum. The crude product was filtered through silica gel (pentane, 500 mL) to give the title compound (2.70 g, 12.0 mmol, 80%) as a yellowish oil R 0.56 (pentane). ... 

Under the nitrogen protection, 2-oxo-cyclohexane carboxylate 2.2.11 (1.4 g, 9 mmol) was dissolved in chloroform (30 mL) at room temperature, pyridine (2.5 mL, 31 mmol) was slowly added, and the reaction was stirred. The substrate 2.2.10 (4.5 g, 9 mmol) was dissolved in chloroform (30 mL) and added to the reaction dropwise. The reaction was heated to 40 °C for 3 h. Then, TLC showed that the reaction was completed. The reaction was cooled to 0 °C using the ice water bath, and then, 2 N H2SO4 (20 mL) was slowly added. After vacuum filtration through Cehte and liquid separation, the aqueous phase was extracted with chloroform (3 x 50 mL). The organic phases were combined, washed with saturated brine (50 mL), dried over anhydrous sodium sulfate, and filtered. The solvent was removed by rotary evaporator under reduced pressure, and the resulting crude product was separated and purified by flash column chromatography (PE/ EA = 5 1), the desired product was obtained as 2.2 g white solid (Rf— 0.20 PE/ EA = 15 1), yield 95 %. 

Under the protection of nitrogen, the compound 2.2.30 (500 mg, 1.36 mmol) was dissolved in AcOH (10 mL), and then, Pb(OAc)4 (3.1 g, 6.8 mmol) was added at 0 °C. The reaction was stirred for 1 h at 0 °C. TEC showed that the reaction was completed. Ethylene glycol (5 mL) was added to quench the reaction. The solid was filtered off and washed with ethyl acetate (1(X) mL). The organic phase was reserved and washed with saturated sodium bicarbonate (3 x 50 mL). The water phase was extracted with ethyl acetate (3 x 50 mL). The combined organic phase was dried over anhydrous sodium sulfate. After filtration, the solvent was removed by a rotary evaporator, and the resulting crude product was isolated and purified by flash column chromatography (PE/EA = 5 1) to give 2.2.37 (275 mg) and 2.2.38 (135 mg) as white solid, total yield 92 %. 

Under the protection of nitrogen, the compound 3.6 (332 mg, 1.0 mmol) was dissolved in methanol (10 mL) and tetrahydrofuran (10 mL) and cooled to 0 °C then, tetramethylammonium borohydride (356 mg, 4.0 mmol) was added. The reaction was heated to room temperature and stirred for 24 h. Saturated ammonium chloride solution (10 mL) was slowly added to quench the reaction. The solvent was removed by rotary evaporator and diluted with ethyl acetate (50 mL). The aqueous phase was extracted with ethyl acetate (3 x 50 mL) and washed with saturated brine (20 mL). The combined organic phases were dried over Na2S04 and hltered. Solvent was removed by rotary evaporator. The resulting crude product was purihed by hash silica gel column chromatography (EA/HA = 1 6) to give 274 mg white solid (Rf— 0.50, EA/HA = 1 6), yield 81 %. 46 mg raw material 3.6 was recovered. 

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