(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol CAS 127852-28-2
(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol Basic informationUses Preparation
| Product Name: | (R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol |
| Synonyms: | (R)-BIS-3,5-TRIFLUOROMETHYL-1-PHENYLETHANOL;Rolapitant Intermediate 3;(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol127852-28-2;(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol,99%e.e.;Fosaprepitant Impurity 25;Aprepitant Impurity 49;(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol（Aprepitant）;(R)-1-[3,5-BIS(TRIFLUORO-METHYL)-PHENYL]ETHANOL 98% |
| CAS: | 127852-28-2 |
| MF: | C10H8F6O |
| MW: | 258.16 |
| EINECS: | 603-245-7 |
| Product Categories: | API intermediates;Alcohols, Hydroxy Esters and Derivatives;Chiral Compounds;127852-28-2 |
| Mol File: | 127852-28-2.mol |
(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol Chemical Properties
| Melting point | 53-58℃ |
| Boiling point | 175.8±35.0 °C(Predicted) |
| density | 1.376±0.06 g/cm3(Predicted) |
| storage temp. | -20°C Freezer |
| solubility | Acetonitrile (Slightly), Chloroform (Slightly) |
| pka | 13.99±0.20(Predicted) |
| form | Powder |
| color | White |
| Optical Rotation | [α]/D +27±1°, c = 1 in acetonitrile |
| λmax | 272nm(MeOH)(lit.) |
| InChI | InChI=1/C10H8F6O/c1-5(17)6-2-7(9(11,12)13)4-8(3-6)10(14,15)16/h2-5,17H,1H3/t5-/s3 |
| InChIKey | MMSCIQKQJVBPIR-RXMQYKEDSA-N |
| SMILES | C(C1C=C([C@H](O)C)C=C(C(F)(F)F)C=1)(F)(F)F |&1:4,r| |
| CAS DataBase Reference | 127852-28-2(CAS DataBase Reference) |
Safety Information
| Hazard Codes | Xi,Xn |
| Risk Statements | 36/37/38-52/53-22 |
| Safety Statements | 26-36/37/39-61 |
| WGK Germany | 3 |
| Hazard Note | Irritant |
| HS Code | 29062990 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral |
| Uses | (R)-[3,5-bis (trifluoromethyl) phenyl] ethanol is an important chiral intermediate for the synthesis of novel chemotherapeutic and antiemetic drugs NK-1 receptor antagonists. Antidepressants have good potential efficacy in treating a range of central and peripheral nervous system depressions. |
| Preparation | At present, the methods for preparing optically pure (R)-[3,5-bis (trifluoromethyl) phenyl] ethanol include chemical methods and biological methods. Chemical synthesis requires the use of expensive transition metal Ru and other chemical catalysts, complicated steps, harsh reaction conditions, high energy consumption, large pollution, and low yield. Biological law is the use of free enzymes or whole cells for catalytic preparation. It has the characteristics of mild reaction conditions, high catalytic efficiency, and strong specificity. |
| Chemical Properties | White fine crystalline powder |
| Uses | (R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol is an intermediate in the synthesis of Aprepitant (A729800), a novel selective neurokinin-1 (NK-1) receptor antagonist. In vitro studies using human liver microsomes indicate that Aprepitant is metabolised primarily by CYP3A4 with minor metabolism by CYP1A2 and CYP2C19, and no metabolism by CYP2D6, CYP2C9, or CYP2E1. Antiemetic. |
| General Description | (R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol is a key intermediate for the synthesis of aprepitant, a potent human neurokinin-1 (NK-1) receptor. |
| Synthesis | 30071-93-3 7480-35-5 368-63-8 The general procedure for the synthesis of 1-[3,5-bis(trifluoromethyl)phenyl]ethanol from 3,5-bis(trifluoromethyl)phenylacetophenone and cis-1-amino-2,3-dihydro-1H-inden-2-ol was as follows: in Example 5, [RuCl2(p-cymene)]2 (18.4 g), (1S,2R)- cis-1-amino-2-inden-2-ol (9.0 g) and 1- (3,5-bis(trifluoromethyl)phenyl)ethan-1-one (3 kg) were dissolved in 2-propanol (21 L), stirred for 30 min and thoroughly degassed under vacuum. A 5M sodium hydroxide solution (28mL) was then added and the mixture was aged for 4-6 hours to ensure complete conversion of the feedstock. Upon completion of the reaction, the mixture was poured into 1N HCl (21L) and extracted with heptane (2 x 10.5L). The organic layers were combined, washed with brine, and 1,4-diazabicyclo[2.2.2]octane (740 g) was added. The solution was concentrated to nearly 4 mL/g of alcohol (KF < 200 μg/mL; 2-propanol < 5 vol%). The mixture was inoculated at 40°C and allowed to cool slowly to room temperature to form crystalline species, which were then further cooled to 0°C. The crystalline product was collected by filtration, washed with cold heptane and dried to give the DABCO complex in 75-80% yield and ee value >99%. |
| References | [1] Patent: US2002/22725, 2002, A1 [2] Patent: US2002/52493, 2002, A1 [3] Patent: US2002/52494, 2002, A1 [4] Patent: US6432952, 2002, B1 [5] Patent: US2003/215456, 2003, A1 |
(R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethanol Preparation Products And Raw materials
| Raw materials | (R)-[3,5-bis(trifluoromethyl)phenyl]ethanol-->3',5'-Bis(trifluoromethyl)acetophenone-->(R)-O-ACETYL-1-[3,5-BIS(TRIFLUOROMETHYL)PHENYL]ETHANOL-->1-AMINO-2-HYDROXYINDANE-->Sodium hydroxide-->Isopropyl alcohol |
