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 (36 mL, 78 mmol) in THF (250 mL) was added DMPU (30.5 g, 238 mmol) dropwise (not allowing the temperature to exceed −65° C.), followed by an addition of a solution of dimethyl cyclohexane-1,3-dicarboxylate (11.9 g, 59.5 mmol) in THF (50 mL) at −78° C. over 20 min. After stirring at −78° C. for one hour, 1-bromo-2-chloroethane (11.1 g, 77.4 mmol) was added and the reaction mixture was slowly warmed up to room temperature overnight. After quenched with Sat. NH4Cl (100 mL), the mixture was concentrated under reduced pressure. The resulting residue was diluted with water (200 mL) and extracted with dichloromethane (4×100 mL). The combined organic layer was washed with water (100 mL) and brine (100 mL), dried over MgSO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate: 20/1) to afford 11.7 g (75%) of dimethyl 1-(3-chloropropyl)cyclohexane-1,3-dicarboxylate as a yellow oil. ESI-MS m/z: 263 (M+H)+.

Provenance & Evidence