Synthesis 2017; 49(11): 2394-2401
DOI: 10.1055/s-0036-1588733
psp
© Georg Thieme Verlag Stuttgart · New York

Synthesis and Properties of 2-Oxa-6-azaspiro[3.3]heptane Sulfonate Salts

Richard N. S. van der Haas*
a   Mercachem Process Research B.V., Kerkenbos 1013, 6546BB Nijmegen, The Netherlands
,
Jeroen A. Dekker
a   Mercachem Process Research B.V., Kerkenbos 1013, 6546BB Nijmegen, The Netherlands
,
Jorma Hassfeld
b   Bayer Pharma AG, Chemical Development Wuppertal, Friedrich-Ebert-Strasse 217–333, 42117 Wuppertal, Germany   Email: Richard.vanderHaas@mercachem.com
,
Anastasia Hager
b   Bayer Pharma AG, Chemical Development Wuppertal, Friedrich-Ebert-Strasse 217–333, 42117 Wuppertal, Germany   Email: Richard.vanderHaas@mercachem.com
,
Peter Fey
b   Bayer Pharma AG, Chemical Development Wuppertal, Friedrich-Ebert-Strasse 217–333, 42117 Wuppertal, Germany   Email: Richard.vanderHaas@mercachem.com
,
Philipp Rubenbauer
b   Bayer Pharma AG, Chemical Development Wuppertal, Friedrich-Ebert-Strasse 217–333, 42117 Wuppertal, Germany   Email: Richard.vanderHaas@mercachem.com
,
Eric Damen
a   Mercachem Process Research B.V., Kerkenbos 1013, 6546BB Nijmegen, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 13 December 2016

Accepted after revision: 31 January 2017

Publication Date:
02 March 2017 (online)


Abstract

An improved synthesis of the bicyclic spiro compound 2-oxa-6-azaspiro[3.3]heptane is presented. While this compound is often isolated as an oxalate salt, its isolation as a sulfonic acid salt yields a more stable and more soluble product. With these improved properties access to a wider range of reaction conditions with the spirobicyclic 2-oxa-6-azaspiro[3.3]heptane has been enabled.

 
  • References

  • 1 Carreira EM, Fessard TM. Chem. Rev. 2014; 114: 8257-8257
    • 2a Casaubon RL, Narayan R, Oalmann C, Vu CB. Patent PCT Int. Appl. WO2013059587, 2013
    • 2b Burns CJ. Patent PCT Int. Appl. WO2014000032, 2014
    • 2c Bentley JM, Brookings DC, Brown JA, Cain TP, Gleave LJ, Heifetz A, Jackson VE, Johnstone C, Leigh D, Madden J, Porter JR, Selby MD, Zhu Z. Patent PCT Int. Appl. WO2014009296, 2014
  • 3 Golden M, Legg D, Milne D, Bharadwaj AM, Deepthi K, Gopal M, Dokka N, Nambiar S, Ramachandra P, Santhosh U, Sharma P, Sridharan R, Sulur M, Linderberg M, Nilsson A, Sohlberg R, Kremers J, Oliver S, Patra D. Org. Process Res. Dev. 2016; 20: 675-675
    • 4a Burkhard J, Carreira EM. Org. Lett. 2008; 10: 3525-3525
    • 4b Wuitschik G, Rogers-Evans M, Buckl A, Bernasconi M, Märki M, Godel T, Fischer H, Wagner B, Parrilla I, Schuler F, Schneider J, Alker A, Schweizer WB, Müller K, Carreira EM. Angew. Chem. Int. Ed. 2008; 47: 4512-4512
  • 5 Wu H, Peng XJ, Li P, Dong CC, Chen SH, Chen SJ, Ma RJ. Chinese Patent CN102746312, 2011
    • 6a Miller D, Clark P, Melton T. British Patent GB1169027, 1966
    • 6b So far, only the preparation of the p-toluenesulfonate salt 6d from freshly distilled free base 6 has been described, however, the yield was only 26%.
  • 7 The purity assay was determined by quantitative 1H NMR spectroscopy with pentaerythritol as internal standard.
  • 8 Overberger CG, Okamoto Y, Bulacovschi V. Macromolecules 1975; 8: 31-31
  • 9 US Patent 2005282826, 2005: p. 29.