Sodium hydride → 5-chloro-1-(2-methoxy-ethoxymethyl)-6-pyrrolidin-1-yl-1H-benzoimidazole

Temperature

0 °C

To a mixture of 6-chloro-5-pyrrolidin-1-yl-1H-benzoimidazole (0.443 g, 2.00 mmol) and THF (5 mL) was added NaH (96.0 mg, 60% dispersion in mineral oil, 2.40 mmol) at 0° C. After stirring the reaction mixture for 30 min at 0° C., 1-chloromethoxy-2-methoxy-ethane (0.299 g, 2.40 mmol) was added and the mixture was stirred for 18 h. The reaction mixture was quenched with water and the aqueous layer was extracted with EtOAc (3×50 mL). The combined organic layers were washed with brine (2×20 mL), dried, filtered, and concentrated under reduced pressure. The residue was purified (FCC) (0-10% MeOH/DCM) to yield the titled compound as a mixture of regioisomers (0.240 g, 39%) with a purity of 90%. MS (ESI/CI): mass calcd. for C15H20ClN3O2, 309.1; m/z found, 310.1 [M+H]+.

1. stirringthe mixture was stirred for 18 h
2. customThe reaction mixture was quenched with water
3. extractionthe aqueous layer was extracted with EtOAc (3×50 mL)
4. washThe combined organic layers were washed with brine (2×20 mL)
5. customdried
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified (FCC) (0-10% MeOH/DCM)

ORD record

ord-90df5a4aae7040c4bf4be345dbaa16d0

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09073923B2