Synthesis, Table of Contents Synthesis 2021; 53(19): 3573-3577DOI: 10.1055/a-1526-7657 psp Convenient Synthesis of (R)-3-[(tert-Butoxycarbonyl)amino]piperidine and (R)-3-[(tert-Butoxycarbonyl)amino]azepane Authors Author Affiliations 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 Recommend Article Abstract Buy Article(opens in new window) All articles of this category(opens in new window) 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 Key wordsamides - amines - hydrogenation - heterogeneous catalysis - chirality Full Text References References For recent reviews, see: 1a Abdeldayem A, Raouf YS, Constantinescu SN, Moriggl R, Gunning PT. Chem. Soc. Rev. 2020; 49: 2617 1b Zha G.-F, Rakesh KR, Manukumar HM, Shantharam CS, Long S. Eur. J. Med. Chem. 2019; 162: 465 1c Tomović K, Kocić G, Šmelcerović A. Acta Med. Medianae 2019; 58: 50 1d Tomovic K, Lazarevic J, Kocic G, Deljanin-Ilic M, Anderluh A, Smelcerovic A. Med. Res. Rev. 2019; 39: 404 1e Patel HM, Pawara R, Surana SJ. Third Generation EGFR Inhibitors: Overcoming EGFR Resistance and Toxicity Problems. Elsevier; Amsterdam: 2019: 45-128 1f Li N, Wang L.-J, Jiang B, Li X, Guo C, Guo S, Shi D.-Y. Eur. J. Med. Chem. 2018; 151: 145 1g Flick AC, Ding HX, Leverett CA, Kyne RE. Jr, Liu KK.-C, Fink SJ, O’Donnell CJ. J. Med. Chem. 2017; 60: 6480 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 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 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 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 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 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 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 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 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 2i Feng Y, Duan W, Fan S, Zhang H, Zhang S.-Q, Xin M. Bioorg. Med. Chem. 2019; 27: 115035 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 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 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 2m Deng D, Han L, Zhou J, Zhang H, Li Q. Bioorg. Chem. 2017; 75: 357 2n Xu S, Hao Q, Li H, Liu Z, Zhou W. Org. Process Res. Dev. 2017; 21: 585 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 2p Schnapp G, Klein T, Hoevels Y, Bakker RA, Nar H. J. Med. Chem. 2016; 59: 7466 2q Li G, Huan Y, Yuan B, Wang J, Jiang Q, Lin Z, Shen Z, Huang H. Eur. J. Med. Chem. 2016; 124: 103 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 2s Ran Y, Pei H, Shao M, Chen L. Chem. Biol. Drug Des. 2016; 87: 290 2t Li Q, Han L, Zhang B, Zhou J, Zhang H. Org. Biomol. Chem. 2016; 14: 9598 For patent reviews, see: 3a Hussain H, Abbas G, Green IR, Ali I. Expert Opin. Ther. Pat. 2019; 29: 535 3b Costante R, Stefanucci A, Carradori S, Novellino E, Mollica A. Expert Opin. Ther. Pat. 2015; 25: 209 4a Lim J, Altman MD, Brubaker JD, Gibeau CR. PCT Int. Appl WO 2016144848, 2016 ; Chem. Abstr. 2016, 165, 406011. 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. 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. 4d Kanstrup AB, Sams CK, Lundbeck JM, Christiansen LB, Kristiansen M. PCT Int. Appl WO 2003004496, 2003 ; Chem. Abstr. 2003, 138, 106535. 5a Saburi M, Miyamura K, Morita M, Mizoguchi Y, Yoshikawa S, Tsuboyama S, Sakurai T, Tsuboyama K. Bull. Chem. Soc. Jpn. 1987; 60: 141 5b Ishikawa M, Hiraiwa Y, Kubota D, Tsushima M, Watanabe T, Murakami S, Ouchi S, Ajito K. Bioorg. Med. Chem. 2006; 14: 2131 6 Ansari A, Ramapanicker R. J. Org. Chem. 2018; 83: 8161 7 Cochi A, Pardo DG, Cossy J. Org. Lett. 2011; 13: 4442 8 Moon S.-H, Lee S. Synth. Commun. 1998; 28: 3919 9a Petri A, Colonna V, Piccolo O. Beilstein J. Org. Chem. 2019; 15: 60 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 9c Feng Y, Wang Z, Luo Z, Chen M, He F, Liu B, Goldmann S, Zhang L. Org. Process Res. Dev. 2019; 23: 355 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 10a Kadyrov R. ChemCatChem 2018; 10: 170 10b Kadyrov R. Adv. Synth. Cat. 2019; 361: 185 10c Kadyrov R, Moebus K. Adv. Synth. Cat. 2020; 362: 3352 11a Pellegata R, Pinza M, Pifferi G. Synthesis 1978; 614 11b Boyle WJ, Sifniades S, Van Peppen JF. J. Org. Chem. 1979; 44: 4841 11c Winter W, Graudums I, Frankus E. Liebigs Ann. Chem. 1983; 2021 11d Blade-Font A. Tetrahedron Lett. 1980; 21: 2443 11e Stark PA, Thrall BD, Meadows G.-G, Abdel-Monem MM. J. Med. Chem. 1992; 35: 4264 11f Toshima H, Maru K, Saito M, Ichihara A. Tetrahedron 1999; 55: 5793 11g Abe M, Akiyama T, Umezawa Y, Yamamoto K, Nagai M, Yamazaki H, Ichikawab Y, Muraoka Y. Bioorg. Med. Chem. 2005; 13: 785 11h Ishikawa M, Kubota D, Yamamoto M, Kuroda C, Iguchi M, Koyanagi A, Murakami S, Ajito K. Bioorg. Med. Chem. 2006; 14: 2109 11i Ji J, Chen C, Cai J, Wang X, Zhang K, Shi L, Lv H, Zhang X. Org. Biomol. Chem. 2015; 13: 7624 12a Yamada S, Hongo C, Yoshioka R, Chibata I. J. Org. Chem. 1983; 48: 843 12b Baum R, Smith GG. J. Am. Chem. Soc. 1986; 108: 7325 12c Ebbers EJ, Ariaans GJ. A, Houbiers JP. M, Bruggink A, Zwanenburg B. Tetrahedron 1997; 53: 9417 13 Ignat’ev NV, Barthen P, Kucheryna A, Willner H, Sartori P. Molecules 2012; 17: 5319 14 Reiner C, Nicholson GJ, Nagel U, Schurig V. Chirality 2007; 19: 401 15a Yu K.-L, Rajakumar G, Srivastava LK, Mishra RK, Johnson RL. J. Med. Chem. 1988; 31: 1430 15b Chulin AN, Rodionov IL, Baidakova LK, Rodionova LN, Balashova TA, Ivanov VT. J. Pept. Sci. 2005; 11: 175 15c Lanigan RM, Starkov P, Sheppard TD. J. Org. Chem. 2013; 78: 4512 15d Sayes M, Charette AB. Green Chem. 2017; 19: 5060 16a Sudakow A, Papke U, Lindel T. Chem. Eur. J. 2014; 20: 10223 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 16c Sreenivasan U, Mishra RK, Johnson RL. J. Med. Chem. 1993; 36: 256 Supplementary Material Supplementary Material Supporting Information (PDF) (opens in new window)
