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

HRID 408693

Reaction equation

[Cl:1][C:2]1[C:3]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:4][C:5]2[N:9]=[CH:8][NH:7][C:6]=2[CH:10]=1.[H-].[Na+].Cl[CH2:19][O:20][CH2:21][CH2:22][O:23][CH3:24]>C1COCC1>[Cl:1][C:2]1[C:3]([N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:4][C:5]2[N:9]([CH2:19][O:20][CH2:21][CH2:22][O:23][CH3:24])[CH:8]=[N:7][C:6]=2[CH:10]=1

Participants

Conditions

Temperature: 0 °C

Procedure

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]+.

Workup

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

Sources & evidence

ORD record: ord-e81f870bd54b451985dc101c3ea04261
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759345B2

Linked notes

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