Efficient one-pot synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio-containing side chain of the new broad-spectrum carbapenem antibiotic ertapenem.
An efficient synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio containing side chain of ertapenem (MK-0826) is described. Starting material N-(O,O-diisopropyl phosphoryl)-trans-4-hydroxy-L-proline is converted in a one-pot process to (2S)-cis-3-[[(4-mercapto-2-pyrrolidinyl)carbonyl]amino]benzoic acid monohydrochloride in 70-75% overall yield via a series of six reactions. The development of each of these reactions and the isolation of the product is discussed in detail.
Brands
Karel M J
KM
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. jos_brands@merck.com
Jobson
Ronald B
RB
Conrad
Karen M
KM
Williams
J Michael
JM
Pipik
Brenda
B
Cameron
Mark
M
Davies
Antony J
AJ
Houghton
Peter G
PG
Ashwood
Michael S
MS
Cottrell
Ian F
IF
Reamer
Robert A
RA
Kennedy
Derek J
DJ
Dolling
Ulf-H
UH
Reider
Paul J
PJ
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D000077727:Ertapenem; D007769:Lactams; D015394:Molecular Structure; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015780:Carbapenems; D007769:Lactams; D011759:Pyrrolidines; D047090:beta-Lactams; D000077727:Ertapenem