Water → (3S,4R)-1-((Benzyloxy)carbonyl)-4-hydroxypyrrolidine-3-carboxylic acid

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Reaction Steps

639 g of 1-benzyl 3-ethyl (3S,4R)-4-hydroxypyrrolidine-1,3-dicarboxylate (equivalent to 1.03 mol) was dissolved in 3.02 L of ethanol and 3.02 L of water was added to the solution. While the mixture was stirred and cooled in an ice bath, a sodium hydroxide solution (formed by dissolving 124 g of sodium hydroxide (3.09 mol) in 3.02 L of water) was added dropwise at an internal temperature of 6.0 to 9.8° C. and the mixture was subsequently stirred at an internal temperature of 6 to 10° C. for 1 hour. This was followed by addition of 60.4 g of active carbon. The mixture was then taken out of the ice bath and stirred at room temperature for 30 minutes. The insoluble material was separated by filtration and washed with 1.21 L of water. The filtrate and the wash were combined and concentrated under reduced pressure. To the resulting residue, 3.02 L of diisopropyl ether was added and the mixture was stirred for 5 minutes. Subsequently, the mixture was allowed to standard the aqueous layer (bottom layer) was collected. To the aqueous layer, 3.02 L of diisopropyl ether was added and the mixture was stirred for 5 minutes. The mixture was allowed to stand again and the aqueous layer (bottom layer) was collected. While the aqueous layer was stirred, 0.54 L of 6 mol/L hydrochloric acid was added dropwise (pH changed from 12.8 to 1.5). To the resulting mixture, 4.83 L of ethyl acetate and 1.21 kg of sodium chloride were added and the mixture was stirred for 5 minutes. The mixture was then allowed to stand and the organic layer (top layer) was collected. To the organic layer, 3.02 L of 28% brine was added and the mixture was stirred for 5 minutes. The mixture was then allowed to stand again and the organic layer (top layer) was collected. To the organic layer, 302 g of anhydrous sodium sulfate was added and the mixture was stirred for 1 hour. The resulting solid was separated by filtration and washed with 0.90 L of ethyl acetate. The filtrate and the wash were combined and concentrated under reduced pressure to give 620 g of a crude product of the title compound as a pale brown solid. This product was used in the subsequent step without further purification.

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