Chemical Properties
clear yellow to orange-brown viscous liquid
Uses
(R)-Pyrrolidin-3-ol is used in preparation of allosteric BCR-ABL bifunctional proteolysis targeting chimera compounds.
Synthesis
The general procedure for the synthesis of 3-hydroxypyrrolidine from L-hydroxyproline is as follows:
Example 1: Synthesis of (R)-3-pyrrolidinol
To a 1 liter reaction vessel was added (4R)-hydroxy-L-proline (250 g, 1.907 mol), 2-cyclohexen-1-one (18.3 g, 0.1907 mol), and polyethylene glycol (750 mL, 400 average molar mass). The reaction was carried out by stirring the mixture under nitrogen protection at 150-160 °C. After 10 h, the reaction was judged complete when the reaction mixture changed from a suspension to a homogeneous phase. The yield of (R)-3-pyrrolidinol was 89.3% as determined by gas chromatographic analysis. Subsequently, the reaction solution was subjected to decompression distillation at the same temperature to collect fractions with boiling points of 100-120 °C (pressure 6-40 hPa) to give (R)-3-pyrrolidinol (120.4 g, 72.5% yield, 99.6% chemical purity, 99.9% optical purity ee).
Purification Methods
The (±)-isomer is purified by repeated distillation ( b 102-104o/12mm, 108-110o/18mm), and the (±)-picrate crystallises from EtOH with m 140-141o. The R(+)-enantiomer has b 70o/0.6mm and [] D +5.6o (c 3.63, MeOH). Its hydrochloride has a negative rotation and its dimethiodide has m 230o and [] 24 -8.02o. [Suyama & Kanno Yakugaku Zasshi (J Pharm Soc Japan) 85 531 1965, Uno et al. J Heterocycl Chem 24 1025 1987, Flanagan & Joullie Heterocycles 26 2247 1987, Beilstein 21 III/IV 44.]
References
[1] Chemistry Letters, 1986, p. 893 - 896
[2] Patent: CN105153133, 2018, B. Location in patent: Paragraph 0022; 0023; 0024; 0025; 0026
[3] Synthetic Communications, 1993, vol. 23, # 19, p. 2691 - 2699
[4] Synthetic Communications, 1994, vol. 24, # 10, p. 1381 - 1387
[5] Patent: US2005/222430, 2005, A1. Location in patent: Page/Page column 2
