Ammonium Chloride → 2,5-Dichloro-1-(2-methoxy-ethoxymethyl)-6-pyrrolidin-1-yl-1H-benzoimidazole

Temperature

-78 °C

A solution of 5-chloro-1-(2-methoxy-ethoxymethyl)-6-pyrrolidin-1-yl-1H-benzoimidazole (0.221 g, 0.714 mmol) and THF (2.5 mL) was cooled to −78° C. in an acetone/dry ice bath. Lithium diisopropylamide (2.0M solution in THF/heptane/ethylbenzene, 0.90 mL, 1.8 mmol) was added dropwise and the reaction mixture was stirred at −78° C. for 30 min. N-chlorosuccinimide (267 mg, 2.00 mmol) was added at −78° C. and the reaction mixture was warmed to 23° C. and stirred for 2 h. Saturated aqueous NH4Cl (20 mL) was added and the crude product was extracted into EtOAc (3×50 mL). The combined organic layers were washed with brine (50 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (0-100% EtOAc/hexanes) to yield the titled compound (0.240 g, 71%) as a mixture of regioisomers with purity of 70%. MS (ESI/CI): mass calcd. for C15H19Cl2N3O2, 343.1; m/z found, 344.1 [M+H]+.

1. temperaturethe reaction mixture was warmed to 23° C.
2. stirringstirred for 2 h
3. extractionthe crude product was extracted into EtOAc (3×50 mL)
4. washThe combined organic layers were washed with brine (50 mL)
5. customdried
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified (FCC) (0-100% EtOAc/hexanes)

ORD record

ord-299d12a33ed9411eb1377a9c055734cd

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08759345B2