Sodium hydride → 3-tert-butoxycarbonyl-7-chloro-6-(pyridin-2-ylmethoxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Participants

Reaction Conditions

Reaction Steps

Prepare a slurry of sodium hydride (60% in mineral oil, 168 mg, 4.2 mmol) in DMF (4 mL) and heat to 65° C. Add dropwise a solution of 3-tert-butoxycarbonyl-7-chloro-6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (250 mg, 0.84 mmol) in DMF (5 mL) and stir for 1 h. Add a solution of 2-(bromomethyl)-pyridine hydrobromide (256 mg, 1 mmol) in DMF (1 mL), stir at 65° C. for 0.5 h and cool to ambient temperature. Add water (1 mL) and concentrate the reaction mixture to an oily residue. Partition the residue between EtOAc/hexane (1:1) and water. Dry the organic layer over Na2SO4, filter and concentrate. Purify by chromatography on silica gel eluting with hexane/EtOAc (10:1, 5:1 and 3:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(pyridin-2-ylmethoxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil.

Provenance & Evidence