187876-68-2Relevant articles and documents
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.
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.
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,
