Process Development and Pilot-Plant Synthesis of (2-Chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone

Typeset version

 

TY  - JOUR
  - Kopach, Michael E; Kobierski, Michael E; Coffey, D. Scott; Alt, Charles A; Zhang, Tony; Borghese, Alfio; Trankle, William G; Roberts, Dilwyn J; Moynihan, Humphrey; Lorenz, Kurt; McNamara, Oria A; Kissane, Marie; Maguire, Anita R
  - 2010
  - Unknown
  - Organic Process Research ; Development
  - Process Development and Pilot-Plant Synthesis of (2-Chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone
  - Validated
  - WOS: 5 ()
  - 14
  - 5
  - 1229
  - 1238
  - Routes to (2-chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone, 1, an intermediate in the manufacture of NK1-II inhibitor LY686017 are described which produce 1 in > 75\% yield and 95\% purity. A highly selective telescoped ortho lithation/condensation/oxidation process was developed and successfully scaled to the clinical pilot plant to produce 25 kg of 1. For the pilot-plant campaign, the lithiation step was developed to operate at -50 degrees C using commercial lithium diisopropylamide (LOA), and the oxidation step employed catalytic TEMPO as the primary and NaOCI as the terminal oxidant. After completion of the pilot-plant campaign second-generation approaches to 1 were developed to improve process greenness where the lithiation and condensation step were operated as warm as -10 degrees C, the highly efficient AZADO catalyst was used as a substitute for TEMPO in the Anelli-Montanari oxidation, and process mass intensity was reduced 25\%.
  - 10.1021/op100157q
DA  - 2010/NaN
ER  - 
@article{V67960169,
   = {Kopach, Michael E and  Kobierski, Michael E and  Coffey, D. Scott and  Alt, Charles A and  Zhang, Tony and  Borghese, Alfio and  Trankle, William G and  Roberts, Dilwyn J and  Moynihan, Humphrey and  Lorenz, Kurt and  McNamara, Oria A and  Kissane, Marie and  Maguire, Anita R},
   = {2010},
   = {Unknown},
   = {Organic Process Research ; Development},
   = {Process Development and Pilot-Plant Synthesis of (2-Chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone},
   = {Validated},
   = {WOS: 5 ()},
   = {14},
   = {5},
  pages = {1229--1238},
   = {{Routes to (2-chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone, 1, an intermediate in the manufacture of NK1-II inhibitor LY686017 are described which produce 1 in > 75\% yield and 95\% purity. A highly selective telescoped ortho lithation/condensation/oxidation process was developed and successfully scaled to the clinical pilot plant to produce 25 kg of 1. For the pilot-plant campaign, the lithiation step was developed to operate at -50 degrees C using commercial lithium diisopropylamide (LOA), and the oxidation step employed catalytic TEMPO as the primary and NaOCI as the terminal oxidant. After completion of the pilot-plant campaign second-generation approaches to 1 were developed to improve process greenness where the lithiation and condensation step were operated as warm as -10 degrees C, the highly efficient AZADO catalyst was used as a substitute for TEMPO in the Anelli-Montanari oxidation, and process mass intensity was reduced 25\%.}},
   = {10.1021/op100157q},
  source = {IRIS}
}
AUTHORSKopach, Michael E; Kobierski, Michael E; Coffey, D. Scott; Alt, Charles A; Zhang, Tony; Borghese, Alfio; Trankle, William G; Roberts, Dilwyn J; Moynihan, Humphrey; Lorenz, Kurt; McNamara, Oria A; Kissane, Marie; Maguire, Anita R
YEAR2010
MONTHUnknown
JOURNAL_CODEOrganic Process Research ; Development
TITLEProcess Development and Pilot-Plant Synthesis of (2-Chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone
STATUSValidated
TIMES_CITEDWOS: 5 ()
SEARCH_KEYWORD
VOLUME14
ISSUE5
START_PAGE1229
END_PAGE1238
ABSTRACTRoutes to (2-chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone, 1, an intermediate in the manufacture of NK1-II inhibitor LY686017 are described which produce 1 in > 75\% yield and 95\% purity. A highly selective telescoped ortho lithation/condensation/oxidation process was developed and successfully scaled to the clinical pilot plant to produce 25 kg of 1. For the pilot-plant campaign, the lithiation step was developed to operate at -50 degrees C using commercial lithium diisopropylamide (LOA), and the oxidation step employed catalytic TEMPO as the primary and NaOCI as the terminal oxidant. After completion of the pilot-plant campaign second-generation approaches to 1 were developed to improve process greenness where the lithiation and condensation step were operated as warm as -10 degrees C, the highly efficient AZADO catalyst was used as a substitute for TEMPO in the Anelli-Montanari oxidation, and process mass intensity was reduced 25\%.
PUBLISHER_LOCATION
ISBN_ISSN
EDITION
URL
DOI_LINK10.1021/op100157q
FUNDING_BODY
GRANT_DETAILS