HCID 178526012, compound → HCID 178420424, compound

Participants

Reaction Steps

To a stirred mixture of anhydrous ammonium formate (6.87 g, 0.11 mol) and trans-(S)-2-{(R)-2-[4-benzyloxymethyl)cyclohexyl]pyrrolidin-1-yl}-2-phenylethanol (10.7 g, 0.027 mol) in MeOH (135 mL) is added 10% palladium on carbon (0.54 g), and the resulting mixture is stirred at room temperature under nitrogen atmosphere for 2 hours. Anhydrous ammonium formate (3.45 g) and 10% palladium on carbon (0.54 g) are added, and the mixture is stirred at room temperature under nitrogen atmosphere for another 3 hours. The reaction mixture is filtered, and the filtrate is concentrated. The crude residue (18.26 g) is dissolved with 1N HCl and extracted with ether to remove phenethylalcohol. The water layer is neutrized by addition of 2N NaOH and extracted with CH2Cl2. The combined CH2Cl2 layer is washed with brine, dried over magnesium sulfate, filtered and concentrated to give crude trans-(R)-2-[4-benzyloxymethyl)cyclohexyl]pyrrolidine (6.54 g). To a mixture of crude trans-(R)-2-[4-benzyloxymethyl)cyclohexyl]pyrrolidine in EtOH (20 mL), L-tartaric acid (3.59 g, 0.024 mol) is added. The mixture is warmed to 60° C. until the mixture becomes clear, then the mixture is cooled down slowly to room temperature. The resulting precipitate is filtered and rinsed with additional EtOH to afford pure trans-(R)-2-[4-(benzyloxymethyl)cyclohexyl]pyrrolidine tartaric acid salt as off-white crystals. The tartaric acid salt is dissolved in 1N NaOH aq. and extracted with CH2Cl2. The organic layer is dried over magnesium sulfate, filtered and evaporated to afford pure trans-(R)-2-[4-(benzyloxymethyl)cyclohexyl]pyrrolidine.

Provenance & Evidence