(3S,4S)-1-Benzylpyrrolidine-3,4-diol

Chemical Properties

off-white to light brown powder or needles

Uses

(3S,4S)-(+)-1-Benzyl-3,4-pyrrolidinediol can be used:

• As a building block for the preparation of novel chiral crown ethers.
• As an intermediate in the synthesis of (3R,4R)1-benzyl-4-fluoropyrrolidin-3- amine.
• As an intermediate in the preparation of 3-hydroxy-4-pyrrolidinyl analogs of nucleobases.

Synthesis

Tetrahydrofuran (3.6 L) was cooled under nitrogen protection and LiAlH4 (61.2 g, 1.6 mol) was slowly added. Subsequently, a tetrahydrofuran solution of (3R,4R)-1-benzyl-3,4-dihydroxypyrrolidine-2,5-dione (132.7 g, 0.6 mol) was added dropwise to this suspension. The reaction mixture was refluxed for 12 h and cooled to room temperature. In an ice-water bath, ethyl acetate (144 mL), distilled water (61.2 mL), 5% aqueous NaOH solution (61.2 mL), and distilled water (183.6 mL) were added sequentially and slowly dropwise while maintaining vigorous stirring. The reaction mixture was filtered and the filter cake was washed with hot tetrahydrofuran (2 x 1.2 L). The filtrate and washings were combined and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give a light yellow oil. The oil was recrystallized from ethyl acetate to give (3S,4S)-1-benzylpyrrolidine-3,4-diol (82.3 g, 71.0% yield) as a white solid.

References

[1] Tetrahedron, 2007, vol. 63, # 5, p. 1243 - 1253
[2] Angewandte Chemie, 1984, vol. 96, # 6, p. 425 - 426
[3] Patent: CN105693520, 2016, A. Location in patent: Paragraph 0148; 0149; 0159; 0151; 0152; 0153
[4] Patent: EP3067351, 2016, A1. Location in patent: Paragraph 0071; 0072
[5] Chemical and Pharmaceutical Bulletin, 1991, vol. 39, # 9, p. 2219 - 2224