(R)-(-)-3-Pyrrolidinol hydrochloride CAS 104706-47-0
(R)-(-)-3-Pyrrolidinol hydrochloride Basic information
| Product Name: | (R)-(-)-3-Pyrrolidinol hydrochloride |
| Synonyms: | (R)-(-)-3-PYRROLIDINOL HCL;(R)-3-Hydroxypyrrolidine hydrochloride, (R)-3-Pyrrolidinol hydrochloride;(3R)-Pyrrolidin-3-ol hydrochloride;(R)-()-3-Pyrrolidinol hydrochloride ,97%;(R)-3-Hydroxypyrroli;(3R)-3-Hydroxypyrrolidine hydrochloride;(R)-3-Pyrrolindinol hydrochloride;(R)-3-HYDROXYPYRROLIDINE HYDROCHLORIDE |
| CAS: | 104706-47-0 |
| MF: | C4H10ClNO |
| MW: | 123.58 |
| EINECS: | 600-598-9 |
| Product Categories: | Chiral Building Blocks;Simple Alcohols (Chiral);Synthetic Organic Chemistry;Chiral chemicals;Benzenes;chiral;Pyrrole&Pyrrolidine&Pyrroline;pharmacetical;APIs Intermediate;Alcohols and Derivatives;11;1 |
| Mol File: | 104706-47-0.mol |
(R)-(-)-3-Pyrrolidinol hydrochloride Chemical Properties
| Melting point | 104-107 °C(lit.) |
| alpha | -7.6°(20/D, c=3,5, CH3OH) |
| refractive index | -7.8 ° (C=3.5, MeOH) |
| storage temp. | Inert atmosphere,Room Temperature |
| solubility | Soluble in DMSO. |
| form | Solid |
| color | Pale Brown |
| Optical Rotation | [α]20/D 7.6°, c = 3.5 in methanol |
| BRN | 4450078 |
| InChI | InChI=1/C4H9NO.ClH/c6-4-1-2-5-3-4;/h4-6H,1-3H2;1H/t4-;/s3 |
| InChIKey | QPMSJEFZULFYTB-PGMHMLKASA-N |
| SMILES | [C@H]1(O)CNCC1.Cl |&1:0,r| |
| CAS DataBase Reference | 104706-47-0(CAS DataBase Reference) |
Safety Information
| Hazard Codes | Xi |
| Risk Statements | 36/37/38-41-38-37 |
| Safety Statements | 26-36-38 |
| WGK Germany | 3 |
| F | 3-10 |
| HS Code | 29339900 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Eye Irrit. 2 Skin Irrit. 2 STOT SE 3 |
| Chemical Properties | Llight brown crystalline |
| Uses | (R)-(-)-3-Pyrrolidinol hydrochloride is a chiral hydroxy derivative of pyrrlodine used in the preparation of chiral niologically active compounds such as muscarinic receptor antagonists and antimicrobial agents. |
| Uses | (R)-3-Hydroxypyrrolidine hydrochloride is used as a darifenacin Intermediate. |
| Uses | (R)-3-Pyrrolidinol hydrochloride can be used as a building block to synthesize:
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| Synthesis | 51-35-4 104706-47-0 Example 1: Preparation of (R)-3-hydroxypyrrolidine hydrochloride (Formula VII): cyclohexanol (80 liters) was added to the reactor and heated to 155°C. Water was removed by azeotropic distillation until the water content in the solvent did not exceed 0.2% (w/w). The solvent was then cooled to 45 °C and (2S,4R)-4-hydroxy-2-pyrrolidinecarboxylic acid (15 kg) was added and stirred for 10 min. Methyl isobutyl ketone (4.275 liters) was added to the reaction mixture, reheated to 154°C and maintained at this temperature for 5 hours of reaction. The reaction process was monitored by thin layer chromatography. Upon completion of the reaction, the reaction mixture was cooled to 0 °C under nitrogen protection and the pH was adjusted to 1.0-2.0 with ether-HCl (41 l). pH adjustment was completed, the temperature was raised to 25 °C and maintained for 2-3 h. The reaction mixture was then heated to 154 °C and maintained at this temperature for 5 h. The solid product was filtered and the reaction mixture was then heated to 154 °C. The solid product was collected by filtration and washed successively with ethyl acetate (30 liters in two portions) and isopropanol (15 liters). The wet solid was dried by suction for 1-2 hours and then dried under reduced pressure at 55°C for 5 hours to give 10.7 kg (R)-3-hydroxypyrrolidine hydrochloride in 76% yield and 98.5% HPLC purity. |
| 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] Patent: WO2008/100651, 2008, A2. Location in patent: Page/Page column 15; 32-33 [2] Patent: WO2015/110886, 2015, A1. Location in patent: Page/Page column 14 [3] Patent: WO2004/56767, 2004, A1. Location in patent: Page 14 [4] Journal of Medicinal Chemistry, 1992, vol. 35, # 10, p. 1764 - 1773 |
(R)-(-)-3-Pyrrolidinol hydrochloride Preparation Products And Raw materials
| Raw materials | Ethanol-->Sodium hydroxide-->Hydrochloric acid-->Ethyl acetate-->Methanol-->Tetrahydrofuran-->Dichloromethane-->Acetic acid-->PETROLEUM ETHER-->Lithium Aluminum Hydride-->Sodium borohydride-->Acetyl chloride-->Calcium chloride-->Benzylamine-->Cyclohexanol-->HEAVY DISTILLATE-->L-Hydroxyproline-->2-Cyclohexen-1-one-->D(+)-Malic acid |
