Sodium Hydroxide → (2R*,4S*,5S*,6S*)-N,N-dimethyl-5-(2,5-dimethoxybenzyl)amino-6-diphenylmethyl-1-azabicyclo[2.2.2]octane-2-carboxamide

Participants

Reaction Steps

A mixture of compound 34 (2.22 g, 6.13 mmole), 2,5-dimethoxybenzylamine (1.23 g, 7.36 mmole) and CSA (camphersulfonic acid) (20 mg) in toluene (50 ml) was heated at reflux for 24 hours with Dean Stark water separator. The solvent was removed under reduced pressure. The crude imine was used to the next step without purification. A solution of the crude imine in dry THF (20 ml) was added to a solution of NaBH(OAc)3 (3.9 g, 18.4 mmole) and acetic acid (3 ml) in dry THF (20 ml) at 5° C. and stirred at room temperature for 15 hours. The pH value was adjusted to pH=10 by 1N NaOH, and extracted with EtOAc (20 ml×3). The combined organic extracts were washed with brine, dried over MgSO4 and concentrated down. The crude oil was purified by silica gel chromatography (EtOAc:Hexane=1:1 as eluent) to give colorless oil. The oil was purified by recrystallization from MeOH to give compound 35 as colorless crystal (2.21 g, 4.3 mmole, 70%).

Provenance & Evidence