Hydrochloric Acid → 1-Chloro-4-cyclopropyl-2-methoxybenzene

To a solution of 4-bromo-1-chloro-2-methoxy-benzene (1.45 g, 6.55 mmol) in dry tetrahydrofuran (10 ml), was added {1,3-bis(diphenylphosphino)-propane}dichloronickel (II) and cyclopropylmagnesium bromide (46 ml, 0.5 M in tetrahydrofuran, 23 mmols) at room temperature. The solution was stirred at room temperature for 2 hours, and then heated at 65° C. for 48 hours. Aqueous hydrochloric acid solution (1 N, 20 mL) was added, and the mixture was then cooled to room temperature and stirred for 30 minutes. The reaction mixture was partitioned between ethyl acetate and water. The combined organic phase was washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (2% ethyl acetate in hexane) to yield 1-chloro-4-cyclopropyl-2-methoxy-benzene as yellow oily residue (0.81 g, 67%).

1. temperatureheated at 65° C. for 48 hours
2. temperaturethe mixture was then cooled to room temperature
3. stirringstirred for 30 minutes
4. customThe reaction mixture was partitioned between ethyl acetate and water
5. washThe combined organic phase was washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by silica gel chromatography (2% ethyl acetate in hexane)

ORD record

ord-e5340d736c3d47dfb28b737e1d2d0036

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008313B2