Sodium Bicarbonate → HCID 23361310, compound

Participants

Reaction Conditions

Reaction Steps

To a suspension of pentane washed sodium hydride (80% oil dispersion, 2.51 g) in dry dimethylformamide (50 ml) was added 2-(4-methoxyphenyl)pyrrolidine (6.74 g) in dimethylformamide (80 ml), followed by N-(2-chloroethyl)morpholine hydrochloride (7.23 g) and potassium iodide (0.05 g) at ambient temperature. The solution was heated at 110° C. for 1.5 hrs, cooled to ambient temperature, and quenched with saturated aqueous ammonium chloride solution. The mixture was distilled through a Kugelrohr apparatus. The residue was diluted with water and ethyl acetate. The layers were separated, and the aqueous phase was extracted with ethyl acetate (4 times). The combined organic extracts were washed with brine, dried over anhydrous potassium carbonate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography (silica gel, 2% triethylamine/1% methanol/ethyl acetate). The appropriate fractions were collected and concentrated to afford 3.99 g (34.6%) of 1-[2-(4-morpholinyl)ethyl]-2-(4-methoxyphenyl)pyrrolidine. 1-[2-(4-Morpholinyl)ethyl]-2-(4-methoxyphenyl)pyrrolidine (3.75 g) was dissolved in 48% hydrobromic acid (35 ml) and warmed at 110° C. for 5 hrs. The reaction mixture was cooled, neutralized with saturated sodium bicarbonate solution and extracted into dichloromethane (6 times). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography. The appropriate fractions were collected and concentrated to afford 2.36 g (66.0%) of product. The analytical sample was recrystallized from ether/petroleum ether and had mp 107°-108° C.

Provenance & Evidence