The Fit For Purpose Development of S1P1 Receptor Agonist GSK2263167 Using a Robinson Annulation and Saegusa Oxidation to Access an Advanced Phenol Intermediate

A fit for purpose approach has been adopted in order to develop a robust, scalable route to the S1P1 receptor agonist, GSK2263167. The key steps include a Robinson ring annulation followed by a Saegusa oxidation, providing rapid access to an advanced phenol intermediate. Despite the use of stoichiom...

Full description

Saved in:
Bibliographic Details
Published inOrganic process research & development Vol. 17; no. 10; pp. 1239 - 1246
Main Authors Harris, Robert M, Andrews, Benjamin I, Clark, Stacy, Cooke, Jason W. B, Gray, John C. S, Ng, Stephanie Q. Q
Format Journal Article
LanguageEnglish
Published American Chemical Society 18.10.2013
Online AccessGet full text

Cover

Abstract A fit for purpose approach has been adopted in order to develop a robust, scalable route to the S1P1 receptor agonist, GSK2263167. The key steps include a Robinson ring annulation followed by a Saegusa oxidation, providing rapid access to an advanced phenol intermediate. Despite the use of stoichiometric palladium acetate for the Saegusa oxidation, near complete recovery of the palladium has been demonstrated. The remaining steps have been optimised including the removal of all chromatography. An alternative to the Saegusa oxidation is described as well as the development of a flow process to facilitate further scale-up of the amidoxime preparation using hydroxylamine at elevated temperature.
AbstractList A fit for purpose approach has been adopted in order to develop a robust, scalable route to the S1P1 receptor agonist, GSK2263167. The key steps include a Robinson ring annulation followed by a Saegusa oxidation, providing rapid access to an advanced phenol intermediate. Despite the use of stoichiometric palladium acetate for the Saegusa oxidation, near complete recovery of the palladium has been demonstrated. The remaining steps have been optimised including the removal of all chromatography. An alternative to the Saegusa oxidation is described as well as the development of a flow process to facilitate further scale-up of the amidoxime preparation using hydroxylamine at elevated temperature.
Author Clark, Stacy
Andrews, Benjamin I
Cooke, Jason W. B
Gray, John C. S
Ng, Stephanie Q. Q
Harris, Robert M
AuthorAffiliation GlaxoSmithKline Research and Development Ltd
Chemical Development
AuthorAffiliation_xml – name: GlaxoSmithKline Research and Development Ltd
– name: Chemical Development
Author_xml – sequence: 1
  givenname: Robert M
  surname: Harris
  fullname: Harris, Robert M
  email: robert.m.harris@gsk.com
– sequence: 2
  givenname: Benjamin I
  surname: Andrews
  fullname: Andrews, Benjamin I
– sequence: 3
  givenname: Stacy
  surname: Clark
  fullname: Clark, Stacy
– sequence: 4
  givenname: Jason W. B
  surname: Cooke
  fullname: Cooke, Jason W. B
– sequence: 5
  givenname: John C. S
  surname: Gray
  fullname: Gray, John C. S
– sequence: 6
  givenname: Stephanie Q. Q
  surname: Ng
  fullname: Ng, Stephanie Q. Q
BookMark eNo9UM1KAzEYDKJgrR58g-_icfVL0s1uj4vaWiy09Ae8Ldnk23ZLTZYmLb6Nr-pKxdMMM8MMzA27dN4RY_ccHzkK_uTbASJXor1gPZ4KTNJcfVx2HHOZKK7wmt2EsEPEVHHRY9-rLcGoiTDyB5gfD60PBC90or1vP8lF8DUs-ZzDggy1sQsVG--aEGG8fBdCSa4yWIfGbUDDwleNC95B4dxxr2PTUe0sLDVtjkHD7KuxZzV6KIyhEDofCnvSzpCF-Zac38PERTp8km10pFt2Vet9oLs_7LP16HX1_JZMZ-PJczFNNEeMyZCo4pkdDkXOM0OZsNWgrlEpnRuDKseqHghJXNq0yowlgdIMlUprg0YKLmWfPZx7tQnlzh8PrlsrOZa_r5b_r8ofbPhsQQ
ContentType Journal Article
Copyright Copyright © 2013 American Chemical Society
Copyright_xml – notice: Copyright © 2013 American Chemical Society
DOI 10.1021/op400162p
DatabaseTitleList
DeliveryMethod fulltext_linktorsrc
Discipline Engineering
Chemistry
EISSN 1520-586X
EndPage 1246
ExternalDocumentID a652804674
GroupedDBID 123
4.4
55A
7~N
AABXI
ABMVS
ABUCX
ACGFS
ACS
AEESW
AENEX
AFEFF
ALMA_UNASSIGNED_HOLDINGS
AQSVZ
CS3
DU5
EBS
ED
ED~
EJD
F5P
GNL
IH9
JG
JG~
LG6
RNS
ROL
UI2
VF5
VG9
W1F
X
XKZ
ID FETCH-LOGICAL-a100t-9eeb17d992817ce72db4ff066a8cc0680bf423e13d5b7cde203c9665fc0c32133
IEDL.DBID ACS
ISSN 1083-6160
IngestDate Thu Aug 27 13:51:23 EDT 2020
IsPeerReviewed true
IsScholarly true
Issue 10
Language English
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-a100t-9eeb17d992817ce72db4ff066a8cc0680bf423e13d5b7cde203c9665fc0c32133
PageCount 8
ParticipantIDs acs_journals_10_1021_op400162p
ProviderPackageCode JG~
55A
AABXI
GNL
VF5
XKZ
7~N
VG9
W1F
ACS
AEESW
AFEFF
ABMVS
ABUCX
IH9
AQSVZ
ED~
UI2
PublicationCentury 2000
PublicationDate 20131018
PublicationDateYYYYMMDD 2013-10-18
PublicationDate_xml – month: 10
  year: 2013
  text: 20131018
  day: 18
PublicationDecade 2010
PublicationTitle Organic process research & development
PublicationTitleAlternate Org. Process Res. Dev
PublicationYear 2013
Publisher American Chemical Society
Publisher_xml – name: American Chemical Society
SSID ssj0005612
Score 2.1681392
Snippet A fit for purpose approach has been adopted in order to develop a robust, scalable route to the S1P1 receptor agonist, GSK2263167. The key steps include a...
SourceID acs
SourceType Publisher
StartPage 1239
Title The Fit For Purpose Development of S1P1 Receptor Agonist GSK2263167 Using a Robinson Annulation and Saegusa Oxidation to Access an Advanced Phenol Intermediate
URI http://dx.doi.org/10.1021/op400162p
Volume 17
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhV1bS8MwFA5zPqgPXqbidRzQ144k7Xp5HNMpCjqYg72NJD2ZQ2nH1oH4Z_yrJm2nBVGf20LJyeX7cr5zPkIuWVtjgFo6ofJ8x4tc6oTaJlypcK2cMWAyV1s8-LdD727UHtXIxS8ZfM4Md_QsLuGzNbLOA7MoLP7pDr51HH6Z0gxdw4N8umofVP3UHj1qUTk4ejvkalV-U-hFXlrLTLbU-89ujH_90y7ZLoEjdIpI75EaJg2y0V35tTXIVqW14D75MPGH3jSDXjqHvhnNdIFQUQhBqmHA-gwMbsSZId7QmaS2iy7cDO4NWLKl65DrCUDAqkgMbDf-QjwHIolhIHCyXAh4fJsW1kyQpdDJLRjNc-iU-gLoP2OSvkJ--5iXqmR4QIa966furVOaMTiCUZo5EZpdPYijiIcsUBjwWHpaG8AiQqWsgYfUBpkhc-O2DFSMnLrKUKm2VlS53DDhQ1JP0gSPCHieJT7o6lD4HnIdKRqg0tKXgkYo2DFpmmiNy8W0GOd5cs7GX6N-8t8Lp2STW9sKqzwJz0g9my_x3ICHTDbzyfMJf0i-Wg
link.rule.ids 315,783,787,27088,27936,27937,57066,57116
linkProvider American Chemical Society
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV3JTsMwELVYDsCBHbEzB65BdvYcq4pS9koFiVtlO-OCQAkiqYT4GX6VsZtCxQXO2SzbybzJvHmPsWMRGUzQKC_VYeyFWcC91NiCK5eBpTMmQjm2xU3cvQ8vHqKHRibH9sLQICq6U-WK-D_qAoJSyNDCE_91ls1HCQVKC4Pa_R86R9xUNtOA0qGYT1SEpi-1EUhXU_GjszI2InJPdrSR55NRrU70xy9Rxv8NbZUtNzASWuN1X2MzWKyzhfbEvW2dLU0JDW6wT9oN0HmqoVO-QY_mtqwQpvhCUBroi54AQpH4Smk4tIal1dSFs_4lQSfbyA6OXQASJi1jYLX5x1Q6kEUOfYnDUSXh9v1pbNQEdQktZ8hIx6HVsA2g94hF-QLuX6RrXKlxk913Tu_aXa-xZvCk4Lz2MqRvfJJnmZ-KRGPi5yo0hlZFplpbOw9lCKehCPJIJTpHnweaEqvIaK4Dn_LiLTZXlAVuMwhDmwZhYFIZh-ibTPMEtVGxkjxDKXbYIU36oHm1qoGrmvti8D3ru3-dcMQWunfXV4Or85vLPbboW0MLy0lJ99lc_TbCA4IVtTp0--kLVMnGvw
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1NT9wwELUKSEAP5auopS2dA9cgO985RguBlmp3pWUlbivbGVMESlYkK1X8Gf4qY292WXGh53xZEzt-L_PmDWMnIjKYoFFeqsPYC7OAe6mxCVcuAytnTIRyaot-fDkOf99ENx1RtLUwNIiG7tS4JL5d1dPSdA4DgmhkaCGKP11jG1EiXFo2741eJR1xl91MA6JEMV84Ca1eanch3azsIcUOGyyf7qQj96ezVp3qpzfGjP8_vF32qYOTkM_f_x77gNU-2-oturjts48rhoMH7JlmBRR3LRT1IwwpxnWDsKIbgtrASAwFEJrEKdFxyG9r660LF6MrglC2oB2cygAkLErHwHr0zyV1IKsSRhJvZ42Ewb-7ecMmaGvIXWNGOg55pzqA4V-s6gdw_yRdAUuLn9m4OL_uXXpdiwZPCs5bL0P61idllvmpSDQmfqlCYwjGyFRr29ZDGcJrKIIyUoku0eeBJoIVGc114BM_PmTrVV3hFwZhaOkQBiaVcYi-yTRPUBsVK8kzlOIrO6bAT7ol1kxc9twXk2XUj9474SfbHJ4Vkz-_-lff2LZv-1pYaUr6na23jzP8QeiiVcduSr0A4JjJOQ
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=The+Fit+For+Purpose+Development+of+S1P1+Receptor+Agonist+GSK2263167+Using+a+Robinson+Annulation+and+Saegusa+Oxidation+to+Access+an+Advanced+Phenol+Intermediate&rft.jtitle=Organic+process+research+%26+development&rft.au=Harris%2C+Robert+M&rft.au=Andrews%2C+Benjamin+I&rft.au=Clark%2C+Stacy&rft.au=Cooke%2C+Jason+W.+B&rft.date=2013-10-18&rft.pub=American+Chemical+Society&rft.issn=1083-6160&rft.eissn=1520-586X&rft.volume=17&rft.issue=10&rft.spage=1239&rft.epage=1246&rft_id=info:doi/10.1021%2Fop400162p&rft.externalDocID=a652804674
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1083-6160&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1083-6160&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1083-6160&client=summon