Efficient synthesis of (2S,3S)-2-ethyl-3-methylvaleramide using (1S,2S)-pseudoephedrine as a chiral auxiliary

Bin Feng Li; Robert M. Hughes; Jackie Le; Kevin McGee; Donald J. Gallagher; Raymond S. Gross; David Provencal; Jayachandra P. Reddy; Peng Wang; Lev Zegelman; Yuxin Zhao; Scott E. Zook

doi:10.1021/op800260j

Efficient synthesis of (2S,3S)-2-ethyl-3-methylvaleramide using (1S,2S)-pseudoephedrine as a chiral auxiliary

Bin Feng Li, Robert M. Hughes, Jackie Le, Kevin McGee, Donald J. Gallagher, Raymond S. Gross, David Provencal, Jayachandra P. Reddy, Peng Wang, Lev Zegelman, Yuxin Zhao, Scott E. Zook

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

An efficient and scaleable synthesis of (2S,3S)-2-ethyl-3-methylvaleramide (1) has been developed starting from inexpensive and readily available L-isoleucine. The key step in this process is an asymmetric alkylation using (1S,2S)-pseudoephedrine as a chiral auxiliary. A practical procedure was developed to remove the sterically hindered pseudoephedrine auxiliary from the amide. The process consists of eight chemical steps and five isolations without any chromatographic purification. It has been successfully implemented to prepare several multikilogram batches of the target compound 1 in 41% overall yield.

Original language	English
Pages (from-to)	463-467
Number of pages	5
Journal	Organic Process Research and Development
Volume	13
Issue number	3
DOIs	https://doi.org/10.1021/op800260j
State	Published - 15 May 2009
Externally published	Yes

Access to Document

10.1021/op800260j

Cite this

@article{6eb26cbb68324d8a899bd71f7e5fdcc3,

title = "Efficient synthesis of (2S,3S)-2-ethyl-3-methylvaleramide using (1S,2S)-pseudoephedrine as a chiral auxiliary",

abstract = "An efficient and scaleable synthesis of (2S,3S)-2-ethyl-3-methylvaleramide (1) has been developed starting from inexpensive and readily available L-isoleucine. The key step in this process is an asymmetric alkylation using (1S,2S)-pseudoephedrine as a chiral auxiliary. A practical procedure was developed to remove the sterically hindered pseudoephedrine auxiliary from the amide. The process consists of eight chemical steps and five isolations without any chromatographic purification. It has been successfully implemented to prepare several multikilogram batches of the target compound 1 in 41\% overall yield.",

author = "Li, \{Bin Feng\} and Hughes, \{Robert M.\} and Jackie Le and Kevin McGee and Gallagher, \{Donald J.\} and Gross, \{Raymond S.\} and David Provencal and Reddy, \{Jayachandra P.\} and Peng Wang and Lev Zegelman and Yuxin Zhao and Zook, \{Scott E.\}",

year = "2009",

month = may,

day = "15",

doi = "10.1021/op800260j",

language = "English",

volume = "13",

pages = "463--467",

journal = "Organic Process Research and Development",

issn = "1083-6160",

publisher = "American Chemical Society",

number = "3",

}

TY - JOUR

T1 - Efficient synthesis of (2S,3S)-2-ethyl-3-methylvaleramide using (1S,2S)-pseudoephedrine as a chiral auxiliary

AU - Li, Bin Feng

AU - Hughes, Robert M.

AU - Le, Jackie

AU - McGee, Kevin

AU - Gallagher, Donald J.

AU - Gross, Raymond S.

AU - Provencal, David

AU - Reddy, Jayachandra P.

AU - Wang, Peng

AU - Zegelman, Lev

AU - Zhao, Yuxin

AU - Zook, Scott E.

PY - 2009/5/15

Y1 - 2009/5/15

N2 - An efficient and scaleable synthesis of (2S,3S)-2-ethyl-3-methylvaleramide (1) has been developed starting from inexpensive and readily available L-isoleucine. The key step in this process is an asymmetric alkylation using (1S,2S)-pseudoephedrine as a chiral auxiliary. A practical procedure was developed to remove the sterically hindered pseudoephedrine auxiliary from the amide. The process consists of eight chemical steps and five isolations without any chromatographic purification. It has been successfully implemented to prepare several multikilogram batches of the target compound 1 in 41% overall yield.

AB - An efficient and scaleable synthesis of (2S,3S)-2-ethyl-3-methylvaleramide (1) has been developed starting from inexpensive and readily available L-isoleucine. The key step in this process is an asymmetric alkylation using (1S,2S)-pseudoephedrine as a chiral auxiliary. A practical procedure was developed to remove the sterically hindered pseudoephedrine auxiliary from the amide. The process consists of eight chemical steps and five isolations without any chromatographic purification. It has been successfully implemented to prepare several multikilogram batches of the target compound 1 in 41% overall yield.

UR - https://www.scopus.com/pages/publications/66249130038

U2 - 10.1021/op800260j

DO - 10.1021/op800260j

M3 - Article

AN - SCOPUS:66249130038

SN - 1083-6160

VL - 13

SP - 463

EP - 467

JO - Organic Process Research and Development

JF - Organic Process Research and Development

IS - 3

ER -

Efficient synthesis of (2S,3S)-2-ethyl-3-methylvaleramide using (1S,2S)-pseudoephedrine as a chiral auxiliary

Abstract

Access to Document

Fingerprint

Cite this