Dimethylformamide → 1-benzyl 3-ethyl (3R,4S)-4-hydroxypyrrolidine-1,3-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

43 mL of anhydrous N,N-dimethylformamide was added to 1.15 g of benzene ruthenium (II) chloride dimer (2.30 mmol) and 3.00 g of (R)-(−)-BINAP (4.82 mmol) in a stream of argon gas. The mixture was stirred in an oil bath at an external temperature of 95 to 105° C. for 10 minutes. The mixture was then allowed to cool to room temperature. Volatile materials were evaporated under reduced pressure (using a vacuum pump) in an oil bath at an external temperature of 50 to 70° C. to give a catalyst. 33.5 g of 1-benzyl 3-ethyl 4-oxopyrrolidine-1,3-dicarboxylate (115 mmol) and 68 mL of dehydrated dichloromethane were placed in an autoclave and the air in the autoclave was replaced by argon. The catalyst dissolved in 100 mL of dehydrated dichloromethane was then added and the atmosphere in the autoclave was replaced by hydrogen gas three times. The mixture was stirred under a pressurized hydrogen atmosphere (8.83 MPa) at an external temperature of 50 to 60° C. for 4 hours. Heating/stirring was stopped, and the mixture was left overnight. Subsequently, hydrogen gas was released and the mixture was transferred to a different vessel and washed with 30 mL of dehydrated dichloromethane. The mixture was then concentrated under reduced pressure and dried in vacuo at room temperature for 30 minutes to give 42.3 g of a crude product of the title compound as a dark brown oil. This product was used in the subsequent step without further purification.

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