3,3,3-Triethoxyprop-1-yne → ethyl 4-(2-chloro-6-(3,3,3-triethoxyprop-1-ynyl)phenyl)-tetrahydro-2H-pyran-4-carboxylate

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Reaction Conditions

Reaction Steps

A mixture of ethyl 4-(2-bromoethoxy)-2-(2-chloro-6-iodophenyl)butanoate (5.8 g, 12 mmol) and TEA (15 mL, 110 mmol) in 24 mL ACN was degassed by vacuum and back filled with nitrogen 3 times. The mixture was treated with 3,3,3-triethoxyprop-1-yne (2.7 g, 16 mmol), dichlorobis(triphenylphosphine)palladium(ii) (0.17 g, 0.24 mmol) and copper(I) iodide (0.12 g, 0.61 mmol). The mixture was stirred at 55° C. for 2 hours. The mixture was cooled to room temperature, diluted with 100 mL EtOAc, and washed with water (3×20 mL) and then with 20 mL saturated NaCl. The organic layers were dried and concentrated. The crude product was evaporated from 50 mL toluene and dissolved in 50 mL DMF. The mixture was treated with 0.7 g NaH. The mixture was stirred at room temperature for 15 hours. The mixture was quenched with 50 mL water and neutralized with 10% HCl to pH=5. The mixture was then extracted with ether (3×100 mL). The combined organic layers were washed with water (3×20 mL) and saturated NaCl (20 mL), and then dried over anhydrous sodium sulfate and concentrated. The crude product was purified by column chromatography (10% EtOAc/hexane) to give 2.42 g yellow oil. MS m/e: (M+H)+ 487.

Provenance & Evidence