Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction
Matthew Zhao
1
,
James M Mcnamara
2
,
Guo-Jie Ho
2
,
Khateeta Emerson
2
,
Zhiguo J Song
2
,
David M. Tschaen
2
,
Karel M.J. Brands
2
,
Ulf-H Dolling
2
,
Edward J.J. Grabowski
2
,
Paul J Reider
2
,
Ian F. Cottrell
2
,
Michael S. Ashwood
2
,
Brian C Bishop
2
1
Process Research, Merck Sharp & Dohme Research Laboratories, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK.
|
2
Merck
Publication type: Journal Article
Publication date: 2002-08-28
scimago Q2
wos Q1
SJR: 0.737
CiteScore: 6.1
Impact factor: 3.6
ISSN: 00223263, 15206904
PubMed ID:
12227806
Organic Chemistry
Abstract
A streamlined and high-yielding synthesis of aprepitant (1), a potent substance P (SP) receptor antagonist, is described. The enantiopure oxazinone 16 starting material was synthesized via a novel crystallization-induced dynamic resolution process. Conversion of 16 to the penultimate intermediate cis-sec-amine 9 features a highly stereoselective Lewis acid-catalyzed trans acetalization of chiral alcohol 3 with trichloroacetimidate 18 followed by inversion of the adjacent chiral center on the morpholine ring. The six-step process for the synthesis of 9 was accomplished in extremely high overall yield (81%) and with only two isolations.
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67
Total citations:
67
Citations from 2024:
5
(7.46%)
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MLA
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GOST
Copy
Zhao M. et al. Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction // Journal of Organic Chemistry. 2002. Vol. 67. No. 19. pp. 6743-6747.
GOST all authors (up to 50)
Copy
Zhao M., Mcnamara J. M., Ho G., Emerson K., Song Z. J., Tschaen D. M., Brands K. M., Dolling U., Grabowski E. J., Reider P. J., Cottrell I. F., Ashwood M. S., Bishop B. C. Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction // Journal of Organic Chemistry. 2002. Vol. 67. No. 19. pp. 6743-6747.
Cite this
RIS
Copy
TY - JOUR
DO - 10.1021/jo0203793
UR - https://doi.org/10.1021/jo0203793
TI - Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction
T2 - Journal of Organic Chemistry
AU - Zhao, Matthew
AU - Mcnamara, James M
AU - Ho, Guo-Jie
AU - Emerson, Khateeta
AU - Song, Zhiguo J
AU - Tschaen, David M.
AU - Brands, Karel M.J.
AU - Dolling, Ulf-H
AU - Grabowski, Edward J.J.
AU - Reider, Paul J
AU - Cottrell, Ian F.
AU - Ashwood, Michael S.
AU - Bishop, Brian C
PY - 2002
DA - 2002/08/28
PB - American Chemical Society (ACS)
SP - 6743-6747
IS - 19
VL - 67
PMID - 12227806
SN - 0022-3263
SN - 1520-6904
ER -
Cite this
BibTex (up to 50 authors)
Copy
@article{2002_Zhao,
author = {Matthew Zhao and James M Mcnamara and Guo-Jie Ho and Khateeta Emerson and Zhiguo J Song and David M. Tschaen and Karel M.J. Brands and Ulf-H Dolling and Edward J.J. Grabowski and Paul J Reider and Ian F. Cottrell and Michael S. Ashwood and Brian C Bishop},
title = {Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction},
journal = {Journal of Organic Chemistry},
year = {2002},
volume = {67},
publisher = {American Chemical Society (ACS)},
month = {aug},
url = {https://doi.org/10.1021/jo0203793},
number = {19},
pages = {6743--6747},
doi = {10.1021/jo0203793}
}
Cite this
MLA
Copy
Zhao, Matthew, et al. “Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction.” Journal of Organic Chemistry, vol. 67, no. 19, Aug. 2002, pp. 6743-6747. https://doi.org/10.1021/jo0203793.