7,7-Dimethoxyheptanal → (S)-3-(1-Carbamoyl-1,1-diphenylmethyl)-1-(7,7-dimethoxyhept-1-yl)pyrrolidine

Participants

Reaction Conditions

Reaction Steps

To a three-necked 500 mL flask equipped with a mechanical stirrer, a nitrogen inlet, cooling bath, and a thermometer was added (S)-3-(1-carbamoyl-1,1-diphenylmethyl)pyrrolidine (25 g, 0.089 mol) and dichloromethane (200 mL). This mixture was cooled to about 0° C. and 7,7-dimethoxyheptanal (18.6 g, 0.107 mol) was added slowly. During the addition, the reaction temperature was maintained at 5° C. or less. The resulting mixture was stirred at 0 to 5° C. for 1 hour and then sodium triacetoxyborohydride (24.6 g, 0.116 mol) was then added over a 30 minute period. During this addition, the reaction temperature was also maintained at 5° C. or less. The resulting mixture was then stirred at 0 to 5° C. for 6 hours. The reaction was then quenched by adding 5% aqueous potassium carbonate solution (200 mL) while keeping the reaction temperature less than about 20° C. and the resulting mixture was stirred for 1 hour at room temperature. The organic layer was separated and washed with brine (100 mL) and then dried with sodium sulfate (20 g). The organic layer was then concentrated under vacuum to a volume of about 100 mL and this mixture was purified by silica gel chromatography eluting with a gradient of 1 to 10% v/v methanol in dichloromethane. The fractions containing the desired product were combined and concentration under vacuum to afford 28 g of the title intermediate as an oil (72% yield).

Provenance & Evidence