187876-68-2Relevant academic research and scientific papers
An alternative approach to achieve enantiopure (3S)-4-benzyl-3-(4- fluorophenyl)morpholin-2-one: A key intermediate of aprepitant, an NK1 receptor antagonist
Kolla, Naveenkumar,Elati, Chandrashekar R.,Arunagiri, Muthulingam,Gangula, Srinivas,Vankawala, Pravinchandra J.,Anjaneyulu, Yerremilli,Bhattacharya, Apurba,Venkatraman, Sundaram,Mathad, Vijayavitthal T.
, p. 455 - 457 (2007)
An efficient and alternative synthesis of enantiomerically pure (3S)-4-benzyl-3-(4-fluorophenyl)morpholin-2-one (S)-(+)-2), a key intermediate in the synthesis aprepitant (1), is described. The key resolution of N-benzylglycinamide, (±)-9, is achieved via diastereomeric salt crystallization using (+)-di-p-toluoyltartaric acid (DPTTA) as the resolving agent to furnish (S)-(+)-9. Alkylation of (S)-(+)-9 with 2-bromoethanol followed by stereocontrolled cyclization of obtained (S)-(+)-10 afforded the desired enantiomer (S)-(+)-2 with good yields and enantiopurity (>98%). The reaction conditions were optimized to make the process robust in order to implement at the commercial scale.
Preparation method of important intermediate (2S, 3R)-4-benzyl-3-(4-fluorophenyl)morpholine-2-ol for aprepitant synthesis
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, (2017/02/28)
The invention relates to a preparation method of an important intermediate (2S, 3R)-4-benzyl-3-(4-fluorophenyl)morpholine-2-ol for aprepitant synthesis. (2S, 3R)-4-benzyl-3-(4-fluorophenyl)morpholine-2-ol is prepared from 2-(4-fluorophenyl)acetonitrile as an initial raw material through cyclization, oxidation rearrangement, catalytic hydrogenation, benzyl protection, selective reduction and chiral resolution. The preparation method has simple processes, low equipment requirement, less process wastes, less environmental pollution and high product purity.
A convergent approach to the synthesis of aprepitant: a potent human NK-1 receptor antagonist
Elati, Chandrashekar R.,Kolla, Naveenkumar,Gangula, Srinivas,Naredla, Anitha,Vankawala, Pravinchandra J.,Avinigiri, Muttu L.,Chalamala, Subrahmanyeswararao,Sundaram, Venkatraman,Mathad, Vijayavitthal T.,Bhattacharya, Apurba,Bandichhor, Rakeshwar
, p. 8001 - 8004 (2008/03/14)
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
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Page/Page column 38, (2010/11/27)
A process for preparing aprepitant.
Synthesis of N-benzyl-3-(S)-(+)-(4-fluorophenyl)-1,4-oxazin-2-one via a crystallisation induced asymmetric transformation
Alabaster, Ramon J.,Gibson, Andrew W.,Johnson, Simon A.,Edwards, John S.,Cottrell, Ian F.
, p. 447 - 450 (2007/10/03)
The simple and efficient preparation of enantiomerically pure N-benzyl-3-(S)-(+)-(4-fluorophenyl)-1,4-oxazin-2-one by a crystallisation induced asymmetric transformation of its racemate is reported. A key feature of this process is the use of [(1S)-(endo,
