Hydrochloric Acid → (3S,4S)-(+)-1-Benzyl-3,4-pyrrolidindiol

Participants

Reaction Conditions

Reaction Steps

A solution of 32.2 ml (0.6 mole) sulfuric acid in 100 ml DME was added dropwise to a suspension of 66.4 g (0.3 mole) (3R,4R)-1-benzyl-3,4-dihydroxy-2,5-pyrrolidine dione (IIb) and 45.6 g (1.2 moles) sodium boron hydride in 400 ml 1,2-dimethoxyethane (DME) within 2.5 h at room temperature. The mixture was then agitated 4 h at 75° C. After it cooled off, 75 ml MeOH were added and the mixture rotated in to dryness. The residue was taken up in 300 ml water and compounded with 50 ml conc. hydrochloric acid. The mixture was then made alkaline and extracted with 200 ml toluene twice at 65° C. The extraction residue was taken up in 100 ml each of water and toluene, adjusted to be strongly acidic with hydrochloric acid and agitated overnight at room temperature. It was then made alkaline with 30% sodium hydroxide solution. After the addition of 200 ml toluene the organic phase was separated at 65° C. The aqueous phase was extracted again with 200 ml methylene chloride. After the organic phases were rotated in, 85 g oil remained. The latter was taken up in 400 ml ethyl acetate and washed twice with 80 ml water at 65° C. The ethyl-acetate phase was rotated in after drying over sodium sulfate. 60 g residue remained which was recrystallized from 150 ml ethyl acetate. 30.2 g (52.1%) (3S,4S)-1-benzyl-3,4-dihydroxypyrrolidine (IIIb) were obtained in two fractions.

Provenance & Evidence