171338-27-5

Basic information

• Product Name: 2-(R)-[1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(S)-fluorophenylmorpholine
• Synonyms: (2R,3S)-2-[(1R)-1-[3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(4-fluorophenyl)-morpholine;2-(R)-[1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(S)-fluorophenylmorpholine;2-(R)-[1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(S)-fluorophenylmorpholine[Aprepitant-M2];(2R,3S)-2-[(1R)-1-[3,5-Bis(trifluoromethyl]ethoxy]-3-(4-fluorophenyl)morpholine;(2R,3S)-2-((R)-1-(3,5-bis(trifluoroMethyl)phenyl)ethoxy)-3-(4-fluorophenyl)Morpholine;(2R, 3S)-2-(1R)-1-3,5-Bis(trifluoroMethyl) phenyl);Morpholine,2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-, (2R,3S)-;Morpholine,2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-, [2R-[2a(R*),3a]]-
• CAS NO: 171338-27-5
• Molecular Formula: C₂₀H₁₈F₇NO₂
• Molecular Weight: 437.35
• Product Categories: Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 171338-27-5.mol
• Article Data: 17

Chemical Properties

• Boiling Point: 387.856 °C at 760 mmHg
• Flash Point: 188.369 °C
• Appearance: /
• Density: 1.375 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.505
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly, Heated)
• PKA: 6.93±0.60(Predicted)
• CAS DataBase Reference: 2-(R)-[1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(S)-fluorophenylmorpholine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(R)-[1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(S)-fluorophenylmorpholine(171338-27-5)
• EPA Substance Registry System: 2-(R)-[1-(R)-(3,5-Bis(trifluoromethyl)phenyl)ethoxy]-3-(S)-fluorophenylmorpholine(171338-27-5)

Safety Data

• Hazardous Substances Data: 171338-27-5(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Oil

InChI:InChI=1/C20H18F7NO2/c1-11(13-8-14(19(22,23)24)10-15(9-13)20(25,26)27)30-18-17(28-6-7-29-18)12-2-4-16(21)5-3-12/h2-5,8-11,17-18,28H,6-7H2,1H3/t11-,17+,18-/m1/s1

Upstream product

• 1765-93-1 4-fluoroboronic acid 
• 1185503-03-0 4-benzyl-3-(4-fluorophenyl)morpholin-2-ol 
• 1185503-15-4 (+/-)-trans-4-benzyl-2-[2-(3,5-bis-trifluoromethylphenyl)ethoxy]-3-(4-fluorophenyl)morphine 
• 1185503-10-9 (2S,3R)-4-benzyl-3-(4-fluorophenyl)morpholin-2-ol 
• 1025023-03-3 2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-5,6-dihydro-2H-1,4-oxazine 
• 380499-07-0 (2R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-5,6-dihydro-2H-1,4-oxazine 
• 472968-70-0 (2R,3R)-2-[(R)-1-(3,5-Bis-trifluoromethyl-phenyl)-ethoxy]-3-(4-fluoro-phenyl)-4-((R)-1-phenyl-ethyl)-morpholine 
• 380499-06-9 (2R,3R)-2-[(1R)-1-(3,5-bis-trifluoro-methylphenyl)ethoxy]-3-(4-fluorophenyl)morpholine 
• 472968-69-7 2,2,2-Trichloro-acetimidic acid (2R,3R)-3-(4-fluoro-phenyl)-4-((R)-1-phenyl-ethyl)-morpholin-2-yl ester 
• 472968-68-6 (2S,3R)-3-(4-fluorophenyl)-4-[(1R)-1-phenylethyl]-2-morpholinol 
• 327623-36-9 (2S,2αR)-4-benzyl-2-[1-[3,5-bis(trifluoromethyl)phenyl]]ethoxy-morpholin-3-one 
• 502536-97-2 2,2,2-trichloro-acetimidic acid 4-benzyl-3-oxo-morpholin-2-yl ester 
• 502537-07-7 trifluoro-acetic acid 4-benzyl-3-oxo-morpholin-2-yl ester 
• 287930-73-8 4-benzyl-2-hydroxy-morpholin-3-one 

Downstream Products

• 219821-37-1 2-[2-[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]-1-iminoethyl]hydrazinecarboxylic acid methyl ester 
• 172822-29-6 5-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-4-morpholinyl]methyl]-1,2-dihydro-3H-1,2,4-triazol-3-one 
• 171482-05-6 [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine hydrochloride 
• 170729-80-3 aprepitant 
• 171482-05-6 [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine hydrochloride 
• 1404074-27-6 BFM₂-(D)-DTTA 
• 171243-14-4 (2R,3S)-2-({(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}oxy)-4-(4-chlorobut-2-ynyl)-3-(4-fluorophenyl)morpholine 

Relevant articles and documents

Understanding the origin of unusual stepwise hydrogenation kinetics in the synthesis of the 3-(4-fluorophenyl)morpholine moiety of NK1 receptor antagonist aprepitant

An efficient and highly stereoselective one-pot Grignard addition/hydrogenation procedure is a key step in the synthesis of the NK 1 receptor antagonist aprepitant. The critical influence of pH on the nature and stability of the intermediate Grignard adducts, along with their reactivity in the hydrogenation reaction, is described. The observation of a defluorinated impurity under hydrogen-starved conditions led to mechanistic studies that revealed unusual kinetics in the hydrogenation reaction. Detailed analysis of the kinetic profiles under hydrogen-starved conditions indicated the two steps of the reaction, debenzylation of the Grignard adducts and reduction of the incipient imine, occurred in near perfect stepwise fashion wherein the debenzylation reaction was essentially complete before any imine reduction took place. Under hydrogen-saturated conditions the inhibition of the imine reduction was less complete, but the partial buildup of reactive imine intermediate led to a dramatic spike in reaction rate toward the end of reaction. Possible mechanistic rationales to explain these observation are discussed.

Preparation method of aprepitant intermediate

The invention provides a preparation method of an aprepitant intermediate, and belongs to the technical field of chemical synthesis. According to the invention, (2R)-2-[(1R)-1-[3, 5-bis (trifluoromethyl) phenyl] ethyoxyl]-3-bromomorpholine is subjected to Suzuki coupling reaction to obtain (2R, 3S)-2-[(1R)-1-[3, 5-bis (trifluoromethyl) phenyl] ethyoxyl]-3-(4- fluorophenyl) morpholine; reacting (2R, 3S)-2-[(1R)-1-[3, 5-bis (trifluoromethyl) phenyl] ethyoxyl]-3-(4- fluorophenyl) morpholine with hydrochloric acid to obtain the aprepitant intermediate (2R, 3S)-2-[(1R)-1-[3, 5-bis (trifluoromethyl) phenyl] ethoxy]-3-(4-fluorophenyl) morpholine hydrochloride. In the preparation process, environmental humidity and oxygen content do not need to be controlled, hydrogenation is not needed, operation is safer, simpler and more convenient, industrial scale-up production is easy, few byproducts are produced in the reaction process, and the purity of aprepitant prepared from the obtained key intermediate I is higher.

REDUCTION OF ORGANIC COMPOUNDS WITH LOW AMOUNTS OF HYDROGEN

The present invention relates to a process for the reaction of a compound with hydrogen wherein the reaction is conducted using a hydrogen-containing gas comprising up to about 10 vol.% hydrogen and at least about 90 vol.% of an inert gas and wherein the