Hydrochloric Acid → Tert-butyl 3-chloro-4-(3-oxocyclohexyl)benzoate

To a mixture of tert-butyl 4-bromo-3-chlorobenzoate (4.00 g, 13.70 mmol) in anhydrous tetrahydrofuran (40 mL) was added isopropylmagnesium chloride (1.3 M solution in tetrahydrofuran, 13.8 mL, 17.9 mmol) at −40° C. The reaction mixture was warmed to ambient temperature and stirred for 1 hour. To this mixture was then added a solution of copper(I) cyanide (1.35 g, 15.10 mmol) and lithium chloride (1.28 g, 30.20 mmol) in anhydrous tetrahydrofuran (5 mL) at 0° C. The reaction mixture was stirred for 10 minutes at 0° C., then 2-cyclohexen-lone (1.32 mL, 13.70 mmol) and trimethylsilyl chloride (1.74 mL, 13.80 mmol) were added to the reaction mixture. The reaction mixture was stirred for 16 hours at ambient temperature. After addition of 1 N hydrochloric acid (10 mL), the reaction mixture was stirred for 1 hour and then diluted with ethyl acetate (150 mL). The organic phase was washed with 1 N hydrochloric acid (10 mL), brine (10 mL), and dried over anhydrous sodium sulfate. Filtration and concentration of the filtrate gave tert-butyl 3-chloro-4-(3-oxocyclohexyl)benzoate as an oil (4.20 g, quant.), which was used without further purification.

1. stirringThe reaction mixture was stirred for 10 minutes at 0° C.
2. stirringThe reaction mixture was stirred for 16 hours at ambient temperature
3. stirringthe reaction mixture was stirred for 1 hour
4. washThe organic phase was washed with 1 N hydrochloric acid (10 mL), brine (10 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationFiltration and concentration of the filtrate

ORD record

ord-26da672884c148caa964c39dbc668bbf

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2