Download PDF
Synthesis 2021; 53(19): 3573-3577
DOI: 10.1055/a-1526-7657
psp

Convenient Synthesis of (R)-3-[(tert-Butoxycarbonyl)amino]piperidine and (R)-3-[(tert-Butoxycarbonyl)amino]azepane

Renat Kadyrov  ∗
a   Institute of Inorganic Chemistry, Academy of Sciences of the Czech Republic, 25068 Řež, Czech Republic
b   Evonik Resource Efficiency GmbH, Rodenbacher Chaussee 4, 63457 Hanau, Germany
,
Oleg L. Tok
a   Institute of Inorganic Chemistry, Academy of Sciences of the Czech Republic, 25068 Řež, Czech Republic
› Author Affiliations
› Further Information
    Permissions and Reprints All articles of this category


Abstract

(R)-3-[(tert-Butoxycarbonyl)amino]piperidine and (R)-3-[(tert-butoxycarbonyl)amino]azepane were prepared in two steps starting from d-ornithine and d-lysine, respectively. In the key step, N-Boc-protected 3-aminolactams were converted into imido esters by O-alkyl­ation and then hydrogenated to amines, under mild conditions (5 bar H2, room temperature) and without isolation, over a standard hydrogenation catalyst (5% Pt/C).

Key words

amides - amines - hydrogenation - heterogeneous catalysis - chirality

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-1526-7657 and contains full experimental details for 1a and 1b, determination of the enantiomeric excess of 3a and 3b, and 1H and 13C NMR spectra of compounds.
  • Supporting Information


Publication History

Received: 21 May 2021

Accepted: 10 June 2021

Accepted Manuscript online:
10 June 2021

Article published online:
13 July 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References


      • For recent reviews, see:
    • 1a Abdeldayem A, Raouf YS, Constantinescu SN, Moriggl R, Gunning PT. Chem. Soc. Rev. 2020; 49: 2617
      CrossrefPubMed
    • 1b Zha G.-F, Rakesh KR, Manukumar HM, Shantharam CS, Long S. Eur. J. Med. Chem. 2019; 162: 465
      CrossrefPubMed
    • 1c Tomović K, Kocić G, Šmelcerović A. Acta Med. Medianae 2019; 58: 50
      Crossref
    • 1d Tomovic K, Lazarevic J, Kocic G, Deljanin-Ilic M, Anderluh A, Smelcerovic A. Med. Res. Rev. 2019; 39: 404
      CrossrefPubMed
    • 1e Patel HM, Pawara R, Surana SJ. Third Generation EGFR Inhibitors: Overcoming EGFR Resistance and Toxicity Problems. Elsevier; Amsterdam: 2019: 45-128
      CrossrefGoogle Scholar
    • 1f Li N, Wang L.-J, Jiang B, Li X, Guo C, Guo S, Shi D.-Y. Eur. J. Med. Chem. 2018; 151: 145
      CrossrefPubMed
    • 1g Flick AC, Ding HX, Leverett CA, Kyne RE. Jr, Liu KK.-C, Fink SJ, O’Donnell CJ. J. Med. Chem. 2017; 60: 6480
      CrossrefPubMed
    • 1h Vardanyan R. Piperidine-Based Drug Discovery 2017; 127-146
    • 1i Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H. Chem. Rev. 2016; 116: 422
      CrossrefPubMed

      For recent examples of drugs with 3-aminopiperidine and 3-aminoazepane units, see:
    • 2a Cooper M, Llinas A, Hansen P, Caffrey M, Ray A, Sjödin S, Shamovsky I, Wada H, Jensen TJ, Sivars U, Hultin L, Andersson U, Lundqvist S, Gedda K, Jinton L, Krutrök N, Lewis R, Jansson P, Gardelli C. J. Med. Chem. 2020; 63: 9705
      CrossrefPubMed
    • 2b Atobe M, Serizawa T, Yamakawa N, Takaba K, Nagano Y, Yamaura T, Tanaka E, Tazumi A, Bito S, Ishiguro M, Kawanishi M. J. Med. Chem. 2020; 63: 7143
      CrossrefPubMed
    • 2c Liu Y, Hao M, Leggett AL, Gao Y, Ficarro SB, Che J, He Z, Olson CM, Marto JA, Kwiatkowski NP, Zhang T, Gray NS. J. Med. Chem. 2020; 63: 6708
      CrossrefPubMed
    • 2d Evison BJ, Palmer JT, Lambert G, Treutlein H, Zeng J, Nativel B, Chemello K, Zhu Q, Wang J, Teng Y, Tang W, Xu Y, Rathi AK, Kumar S, Suchowerska AK, Parmar J, Dixon I, Kelly GE, Bonnar J. Bioorg. Med. Chem. 2020; 28: 115344
      CrossrefPubMed
    • 2e Fromont C, Atzori A, Kaur D, Hashmi L, Greco G, Cabanillas A, Nguyen HV, Jones DH, Garzón M, Varela A, Stevenson B, Iacobini GP, Lenoir M, Rajesh S, Box C, Kumar J, Grant P, Novitskaya V, Morgan J, Sorrell FJ, Redondo C, Kramer A, Harris CJ, Leighton B, Vickers SP, Cheetham SC, Kenyon C, Grabowska AM, Overduin M, Berditchevski F, Weston CJ, Knapp S, Fischer PM, Butterworth S. J. Med. Chem. 2020; 63: 6784
      CrossrefPubMed
    • 2f Manz TD, Sivakumaren SC, Yasgar A, Hall MD, Davis MI, Seo H.-S, Card JD, Ficarro SB, Shim H, Marto JA, Dhe-Paganon S, Sasaki AT, Boxer MB, Simeonov A, Cantley LC, Shen M, Zhang T, Ferguson FM, Gray NS. ACS Med. Chem. Lett. 2020; 11: 346
      CrossrefPubMed
    • 2g Watterson SH, Liu Q, Beaudoin Bertrand M, Batt DG, Li L, Pattoli MA, Skala S, Cheng L, Obermeier MT, Moore R, Yang Z, Vickery R, Elzinga PA, Discenza L, D’Arienzo C, Gillooly KM, Taylor TL, Pulicicchio C, Zhang Y, Heimrich E, McIntyre KW, Ruan Q, Westhouse RA, Catlett IM, Zheng N, Chaudhry C, Dai J, Galella MA, Tebben AJ, Pokross M, Li J, Zhao R, Smith D, Rampulla R, Allentoff A, Wallace MA, Mathur A, Salter-Cid L, Macor JE, Carter PH, Fura A, Burke JR, Tino JA. J. Med. Chem. 2019; 62: 3228
      CrossrefPubMed
    • 2h Huang J, Deng X, Zhou S, Wang N, Qin Y, Meng L, Li G, Xiong Y, Fan Y, Guo L, Lan D, Xing J, Jiang W, Li Q. Bioorg. Med. Chem. 2019; 27: 644
      CrossrefPubMed
    • 2i Feng Y, Duan W, Fan S, Zhang H, Zhang S.-Q, Xin M. Bioorg. Med. Chem. 2019; 27: 115035
      CrossrefPubMed
    • 2j Londregan AT, Wei L, Xiao J, Lintner NG, Petersen D, Dullea RG, McClure KF, Bolt MW, Warmus JS, Coffey SB, Limberakis C, Genovino J, Thuma BA, Hesp KD, Aspnes GE, Reidich B, Salatto CT, Chabot JR, Cate JH. D, Liras S, Piotrowski DW. J. Med. Chem. 2018; 61: 5704
      CrossrefPubMed
    • 2k Rugel A, Tarpley RS, Lopez A, Menard T, Guzman MA, Taylor AB, Cao X, Kovalskyy D, Chevalier FD, Anderson TJ. C, Hart PJ, LoVerde PT, McHardy SF. ACS Med. Chem. Lett. 2018; 9: 967
      CrossrefPubMed
    • 2l Zhang H, Wang J, Zhao H.-Y, Yang X.-Y, Lei H, Xin M, Cao Y.-X, Zhang S.-Q. Bioorg. Med. Chem. 2018; 26: 3619
      CrossrefPubMed
    • 2m Deng D, Han L, Zhou J, Zhang H, Li Q. Bioorg. Chem. 2017; 75: 357
      CrossrefPubMed
    • 2n Xu S, Hao Q, Li H, Liu Z, Zhou W. Org. Process Res. Dev. 2017; 21: 585
      Crossref
    • 2o Wu W.-L, Hao J, Domalski M, Burnett DA, Pissarnitski D, Zhao Z, Stamford A, Scapin G, Gao Y.-D, Soriano A, Kelly TM, Yao Z, Powles MA, Chen S, Mei H, Hwa J. ACS Med. Chem. Lett. 2016; 7: 498
      CrossrefPubMed
    • 2p Schnapp G, Klein T, Hoevels Y, Bakker RA, Nar H. J. Med. Chem. 2016; 59: 7466
      CrossrefPubMed
    • 2q Li G, Huan Y, Yuan B, Wang J, Jiang Q, Lin Z, Shen Z, Huang H. Eur. J. Med. Chem. 2016; 124: 103
      CrossrefPubMed
    • 2r Imaeda Y, Tawada M, Suzuki S, Tomimoto M, Kondo M, Tarui N, Sanada T, Kanagawa R, Snell G, Behnke CA, Kubo K, Kuroita T. Bioorg. Med. Chem. 2016; 24: 5771
      CrossrefPubMed
    • 2s Ran Y, Pei H, Shao M, Chen L. Chem. Biol. Drug Des. 2016; 87: 290
      CrossrefPubMed
    • 2t Li Q, Han L, Zhang B, Zhou J, Zhang H. Org. Biomol. Chem. 2016; 14: 9598
      CrossrefPubMed

      For patent reviews, see:
    • 3a Hussain H, Abbas G, Green IR, Ali I. Expert Opin. Ther. Pat. 2019; 29: 535
      CrossrefPubMed
    • 3b Costante R, Stefanucci A, Carradori S, Novellino E, Mollica A. Expert Opin. Ther. Pat. 2015; 25: 209
      CrossrefPubMed
    • 4a Lim J, Altman MD, Brubaker JD, Gibeau CR. PCT Int. Appl WO 2016144848, 2016 ; Chem. Abstr. 2016, 165, 406011.
      PubMed
    • 4b Burnett DA, Zhao Z, Cole D, Josien H, Pissarnitski DA, Sasikumar T, Wu W.-L, Domalski M. PCT Int. Appl WO 2012078448, 2012 ; Chem Abstr. 2012, 157, 95636.
      PubMed
    • 4c Hauel N, Himmelsbach F, Langkopf E, Eckhardt M, Maier R, Mark M, Tadayyon M, Kauffmann-Hefner I. PCT Int. Appl WO 2004050658, 2004 ; Chem Abstr. 2004, 141, 54352.
      PubMed
    • 4d Kanstrup AB, Sams CK, Lundbeck JM, Christiansen LB, Kristiansen M. PCT Int. Appl WO 2003004496, 2003 ; Chem. Abstr. 2003, 138, 106535.
      PubMed
    • 5a Saburi M, Miyamura K, Morita M, Mizoguchi Y, Yoshikawa S, Tsuboyama S, Sakurai T, Tsuboyama K. Bull. Chem. Soc. Jpn. 1987; 60: 141
      Crossref
    • 5b Ishikawa M, Hiraiwa Y, Kubota D, Tsushima M, Watanabe T, Murakami S, Ouchi S, Ajito K. Bioorg. Med. Chem. 2006; 14: 2131
      CrossrefPubMed
  • 6 Ansari A, Ramapanicker R. J. Org. Chem. 2018; 83: 8161
    CrossrefPubMed
  • 7 Cochi A, Pardo DG, Cossy J. Org. Lett. 2011; 13: 4442
    CrossrefPubMed
  • 8 Moon S.-H, Lee S. Synth. Commun. 1998; 28: 3919
    Crossref
    • 9a Petri A, Colonna V, Piccolo O. Beilstein J. Org. Chem. 2019; 15: 60
      CrossrefPubMed
    • 9b Feng Y, Luo Z, Sun G, Chen M, Lai J, Lin W, Goldmann S, Zhang L, Wang Z. Org. Process Res. Dev. 2017; 21: 648
      Crossref
    • 9c Feng Y, Wang Z, Luo Z, Chen M, He F, Liu B, Goldmann S, Zhang L. Org. Process Res. Dev. 2019; 23: 355
      Crossref
    • 9d Ford GJ, Kress N, Mattey AP, Hepworth LJ, Baldwin CR, Marshall JR, Seibt LS, Huang M, Birmingham WR, Turner NJ, Flitsch SL. Chem. Commun. 2020; 56: 7949
      CrossrefPubMed
    • 10a Kadyrov R. ChemCatChem 2018; 10: 170
      Crossref
    • 10b Kadyrov R. Adv. Synth. Cat. 2019; 361: 185
      Crossref
    • 10c Kadyrov R, Moebus K. Adv. Synth. Cat. 2020; 362: 3352
      Crossref
    • 11a Pellegata R, Pinza M, Pifferi G. Synthesis 1978; 614
    • 11b Boyle WJ, Sifniades S, Van Peppen JF. J. Org. Chem. 1979; 44: 4841
      Crossref
    • 11c Winter W, Graudums I, Frankus E. Liebigs Ann. Chem. 1983; 2021
    • 11d Blade-Font A. Tetrahedron Lett. 1980; 21: 2443
      Crossref
    • 11e Stark PA, Thrall BD, Meadows G.-G, Abdel-Monem MM. J. Med. Chem. 1992; 35: 4264
      CrossrefPubMed
    • 11f Toshima H, Maru K, Saito M, Ichihara A. Tetrahedron 1999; 55: 5793
      Crossref
    • 11g Abe M, Akiyama T, Umezawa Y, Yamamoto K, Nagai M, Yamazaki H, Ichikawab Y, Muraoka Y. Bioorg. Med. Chem. 2005; 13: 785
      CrossrefPubMed
    • 11h Ishikawa M, Kubota D, Yamamoto M, Kuroda C, Iguchi M, Koyanagi A, Murakami S, Ajito K. Bioorg. Med. Chem. 2006; 14: 2109
      CrossrefPubMed
    • 11i Ji J, Chen C, Cai J, Wang X, Zhang K, Shi L, Lv H, Zhang X. Org. Biomol. Chem. 2015; 13: 7624
      CrossrefPubMed
    • 12a Yamada S, Hongo C, Yoshioka R, Chibata I. J. Org. Chem. 1983; 48: 843
      Crossref
    • 12b Baum R, Smith GG. J. Am. Chem. Soc. 1986; 108: 7325
      Crossref
    • 12c Ebbers EJ, Ariaans GJ. A, Houbiers JP. M, Bruggink A, Zwanenburg B. Tetrahedron 1997; 53: 9417
      Crossref
  • 13 Ignat’ev NV, Barthen P, Kucheryna A, Willner H, Sartori P. Molecules 2012; 17: 5319
    CrossrefPubMed
  • 14 Reiner C, Nicholson GJ, Nagel U, Schurig V. Chirality 2007; 19: 401
    CrossrefPubMed
    • 15a Yu K.-L, Rajakumar G, Srivastava LK, Mishra RK, Johnson RL. J. Med. Chem. 1988; 31: 1430
      CrossrefPubMed
    • 15b Chulin AN, Rodionov IL, Baidakova LK, Rodionova LN, Balashova TA, Ivanov VT. J. Pept. Sci. 2005; 11: 175
      CrossrefPubMed
    • 15c Lanigan RM, Starkov P, Sheppard TD. J. Org. Chem. 2013; 78: 4512
      CrossrefPubMed
    • 15d Sayes M, Charette AB. Green Chem. 2017; 19: 5060
      Crossref
    • 16a Sudakow A, Papke U, Lindel T. Chem. Eur. J. 2014; 20: 10223
      CrossrefPubMed
    • 16b Amblard M, Daffix I, Bergé G, Calmès M, Dodey P, Pruneau D, Paquet J.-L, Luccarini J.-M, Bélichard P, Martinez J. J. Med. Chem. 1999; 42: 4193
      CrossrefPubMed
    • 16c Sreenivasan U, Mishra RK, Johnson RL. J. Med. Chem. 1993; 36: 256
      CrossrefPubMed