171338-27-5

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

• 352-13-6 4-flourophenylmagnesium bromide 
• 287930-75-0 (2R,2αR)-4-benzyl-2-[1-[3,5-bis(trifluoromethyl)phenyl]]ethoxy-morpholin-3-one 
• 934540-47-3 C₂₀H₁₆F₇NO₂ 
• 380499-07-0 (2R)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-5,6-dihydro-2H-1,4-oxazine 
• 1025023-03-3 2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)-5,6-dihydro-2H-1,4-oxazine 
• 1185503-10-9 (2S,3R)-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 
• 1765-93-1 4-fluoroboronic acid 
• 1185503-03-0 4-benzyl-3-(4-fluorophenyl)morpholin-2-ol 
• 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 

Downstream Products

• 170729-80-3 aprepitant 
• 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 
• 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 academic research and scientific papers

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 NK1 receptor antagonist

The invention discloses a preparation method of an NK1 receptor antagonist. According to the invention, chiral resolution adopts a mixed solvent, CaCl2 is added for a reaction in an alkaline environment, CaCl2 does not participate in the reaction but needs to be added in advance for better devitrification, water is added for quenching after the reaction is finished, and CaCl2 is dissolved at the same time, so devitrification efficiency is further improved; and then 5-hydroxymethyl-2,4-dihydro-[1,2,4]triazin-3-one is used as a raw material for synthesis of aprepitant under the catalysis of DBU at room temperature.

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

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

Synthesis of all enantiomerically pure diastereomers of aprepitant

Syntheses of all eight enantiomerically pure diastereomers of aprepitant and assignment of absolute configuration at newly generated stereocenters by NMR and X-ray crystallographic analysis were achieved. Copyrigh

PREPARATION OF MORPHOLINE DERIVATIVES

This invention relates to processes and intermediates for the stereoselective morpholine derivatives. The invention in particular allows the stereoselective preparation of the drugs aprepitant and fosaprepitant.

A convergent approach to the synthesis of aprepitant: a potent human NK-1 receptor antagonist

A simple and convergent approach to enantiomerically pure 5-[[2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy-3-(4-fluorophenyl)morpholin-4-yl]methyl]-1,2-dihydro-1,2,4-triazol-3-one 1, a potent orally active antagonist of the human neurokinin-1 (NK-1) receptor, is described. The synthetic procedure starts from p-fluorobenzaldehyde to access the racemic morpholinone 2 via a modified Strecker synthesis and utilizes a diastereomeric salt resolution technique to accomplish the synthesis of 1 in enantiomerically pure form and good yield.

PREPARATION OF APREPITANT

A process for preparing aprepitant.

Mammalian metabolites of a tachykinin receptor antagonist

This invention is concerned with mammalian metabolites of the compound 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenyl)ethoxy)-3-(S)-(4-fluoro)-phenyl-4-(3-(5-oxo-1H,4H-1,2,4-triazolo)methylmorpholine which is a tachykinin receptor antagonist that is useful