A large-scale synthesis of potent glucokinase activator MK-0941 via selective o -arylation and o -alkylation

Naoki Yoshikawa; Feng Xu; Juan D. Arredondo; Takahiro Itoh

doi:10.1021/op200068c

A large-scale synthesis of potent glucokinase activator MK-0941 via selective o -arylation and o -alkylation

Naoki Yoshikawa, Feng Xu, Juan D. Arredondo, Takahiro Itoh

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

Abstract

An efficient, practical preparation of MK-0941, a potent glucokinase activator, is described. Keys to the success of the synthesis are a highly selective mono-O-arylation of methyl 3,5-dihydroxybenzoate with 2-ethanesulfonyl-5-chloropyridine and the choice of a proper protective group for the subsequent S_N2 O-alkylation. With the thorough understanding of the origins and fate of in-process impurities, the second-generation robust synthesis with a minimum number of operations reproducibly prepares MK-0941 in 56% overall yield with >99% purity.

Original language	American English
Pages (from-to)	824-830
Number of pages	7
Journal	Organic Process Research and Development
Volume	15
Issue number	4
DOIs	https://doi.org/10.1021/op200068c
State	Published - Jul 15 2011
Externally published	Yes

ASJC Scopus subject areas

Physical and Theoretical Chemistry
Organic Chemistry

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title = "A large-scale synthesis of potent glucokinase activator MK-0941 via selective o -arylation and o -alkylation",

abstract = "An efficient, practical preparation of MK-0941, a potent glucokinase activator, is described. Keys to the success of the synthesis are a highly selective mono-O-arylation of methyl 3,5-dihydroxybenzoate with 2-ethanesulfonyl-5-chloropyridine and the choice of a proper protective group for the subsequent SN2 O-alkylation. With the thorough understanding of the origins and fate of in-process impurities, the second-generation robust synthesis with a minimum number of operations reproducibly prepares MK-0941 in 56% overall yield with >99% purity.",

author = "Naoki Yoshikawa and Feng Xu and Arredondo, {Juan D.} and Takahiro Itoh",

year = "2011",

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doi = "10.1021/op200068c",

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AU - Yoshikawa, Naoki

AU - Xu, Feng

AU - Arredondo, Juan D.

AU - Itoh, Takahiro

PY - 2011/7/15

Y1 - 2011/7/15

N2 - An efficient, practical preparation of MK-0941, a potent glucokinase activator, is described. Keys to the success of the synthesis are a highly selective mono-O-arylation of methyl 3,5-dihydroxybenzoate with 2-ethanesulfonyl-5-chloropyridine and the choice of a proper protective group for the subsequent SN2 O-alkylation. With the thorough understanding of the origins and fate of in-process impurities, the second-generation robust synthesis with a minimum number of operations reproducibly prepares MK-0941 in 56% overall yield with >99% purity.

AB - An efficient, practical preparation of MK-0941, a potent glucokinase activator, is described. Keys to the success of the synthesis are a highly selective mono-O-arylation of methyl 3,5-dihydroxybenzoate with 2-ethanesulfonyl-5-chloropyridine and the choice of a proper protective group for the subsequent SN2 O-alkylation. With the thorough understanding of the origins and fate of in-process impurities, the second-generation robust synthesis with a minimum number of operations reproducibly prepares MK-0941 in 56% overall yield with >99% purity.

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JF - Organic Process Research and Development

IS - 4

ER -

A large-scale synthesis of potent glucokinase activator MK-0941 via selective o -arylation and o -alkylation

Abstract

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