1-Bromo-2-Chloroethane → Dimethyl 1-(3-chloropropyl)cyclohexane-1,3-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a pre-cooled (−78° C.) solution of lithium diisopropylamide (94 mL, 188 mmol) in anhydrous THF (250 mL) was added DMPU (76 g, 600 mmol) dropwise, not allowing the temperature to exceed −65° C., followed by an addition of a solution of dimethyl cyclohexane-1,3-dicarboxylate (25 g, 125 mmol) in anhydrous THF (50 mL) at −78° C. over 20 min. After stirring at −78° C. for one hour, 1-bromo-2-chloroethane (25 g, 175 mmol) was added and the reaction was slowly warmed up to room temperature overnight. After quenched with saturated NH4Cl (100 mL), the reaction mixture was concentrated under reduced pressure and then diluted with water (200 mL). The resulting aqueous mixture was extracted with DCM (4×100 mL) and the combined organic phase was washed with water (100 mL) and brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20/1) to afford 23 g (70%) of the title compound, dimethyl 1-(3-chloropropyl)cyclohexane-1,3-dicarboxylate as a yellow oil. ESI-MS m/z: 263 (M+H)+.

Provenance & Evidence