title: Efficient one-pot synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio-containing side chain of the new broad-spectrum carbapenem antibiotic ertapenem.
abstract: 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.
authors.affiliation: Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. jos_brands@merck.com
authors.forename: Karel M J
authors.initials: KM
authors.lastname: Brands
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Jobson
authors.forename: Karen M
authors.initials: KM
authors.lastname: Conrad
authors.forename: J Michael
authors.initials: JM
authors.lastname: Williams
authors.forename: Brenda
authors.initials: B
authors.lastname: Pipik
authors.forename: Mark
authors.initials: M
authors.lastname: Cameron
authors.forename: Antony J
authors.initials: AJ
authors.lastname: Davies
authors.forename: Peter G
authors.initials: PG
authors.lastname: Houghton
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ashwood
authors.forename: Ian F
authors.initials: IF
authors.lastname: Cottrell
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reamer
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: Ulf-H
authors.initials: UH
authors.lastname: Dolling
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Reider
mesh_terms: 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
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015780:Carbapenems; D007769:Lactams; D011759:Pyrrolidines; D047090:beta-Lactams; D000077727:Ertapenem