Chloroiodomethane → 2-Chloro-1-(1-(2,4-dichloro-5-methoxyphenyl)piperidin-4-yl)ethanone

Temperature

-70 °C

An oven-dried, 50-mL 2-neck round bottom flask containing a stir bar was fitted with an inert gas inlet and a rubber septum and placed under argon. The flask was charged with ethyl 1-(2,4-dichloro-5-methoxyphenyl)piperidine-4-carboxylate (233 mg, 0.701 mmol) and anhydrous THF (5 mL) and chloroiodomethane (0.102 mL, 1.403 mmol). The mixture was cooled to −70° C. (internal temperature). Once at the prescribed temperature, a solution of methyllithium (0.877 mL of 1.6 M in Et2O, 1.403 mmol) was added dropwise to the mixture via syringe over 5 min. At the conclusion of this period, the mixture was stirred at −70° C. (internal temperature) for 1.5 h and then quenched by adding saturated NH4Cl (2 mL). The pH of the mixture was adjusted to pH 7.5 by careful addition of 2 M HCl. Once at the prescribed pH, the mixture was extracted with EtOAc (25 mL). The aqueous phase was back-extracted with EtOAc and the combined extracts washed with brine, dried (MgSO4) and concentrated on a rotary evaporator to give 2-chloro-1-(1-(2,4-dichloro-5-methoxyphenyl)piperidin-4-yl)ethanone (242 mg). LC-MS: 336.24, [M+H]+; tR=3.84 min (b).

1. additionAn oven-dried, 50-mL 2-neck round bottom flask containing a stir bar
2. customwas fitted with an inert gas inlet
3. customquenched
4. additionby adding saturated NH4Cl (2 mL)
5. additionThe pH of the mixture was adjusted to pH 7.5 by careful addition of 2 M HCl
6. extractionOnce at the prescribed pH, the mixture was extracted with EtOAc (25 mL)
7. extractionThe aqueous phase was back-extracted with EtOAc
8. washthe combined extracts washed with brine
9. dry with materialdried (MgSO4)
10. concentrationconcentrated on a rotary evaporator

ORD record

ord-dac81aa92a6146eb9579c083767e09e3

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354432B2