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

Temperature

-78 °C

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)+.

1. customto exceed −65° C.
2. temperaturethe reaction was slowly warmed up to room temperature overnight
3. customAfter quenched with saturated NH4Cl (100 mL)
4. concentrationthe reaction mixture was concentrated under reduced pressure
5. additiondiluted with water (200 mL)
6. extractionThe resulting aqueous mixture was extracted with DCM (4×100 mL)
7. washthe combined organic phase was washed with water (100 mL) and brine (100 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by column chromatography (silica gel, petroleum ether/ethyl acetate=20/1)

ORD record

ord-a8d3b8f4fc22451781f9bd46dab95047

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09212165B2