Title:
METHOD FOR CONTINUOUS SYNTHESIS OF PROPELLANE COMPOUNDS
Document Type and Number:
WIPO Patent Application WO/2020/252661
Kind Code:
A1
Abstract:
A method for the continuous synthesis of propellane compounds, comprising the following steps: using 1,1-dibromo-2,2-chloromethyl cyclopropane or a derivative thereof as a raw material, preparing propellane compounds by means of continuous reaction and ring fusion with a metal lithium reagent. The present method uses a continuous reaction device, continuous feeding, continuous reaction, continuous transfer, and continuous quenching, and the post-treatment can even obtain a separation yield of more than 90%, implementing highly efficient preparation of propellanes. In addition, the present method shortens the reaction time, solving the problem of products in scaled-up production being unstable in alkaline conditions and deteriorating with long reaction times, greatly reducing the risk of using lithium reagent in the reaction, and being more conducive to scaled-up production.
Inventors:
HONG HAO (US)
ZHANG ENXUAN (CN)
LU JIANGPING (CN)
WEI FULIANG (CN)
YANG SIHANG (CN)
ZHANG ENXUAN (CN)
LU JIANGPING (CN)
WEI FULIANG (CN)
YANG SIHANG (CN)
Application Number:
PCT/CN2019/091732
Publication Date:
December 24, 2020
Filing Date:
June 18, 2019
Export Citation:
Assignee:
JINLIN ASYMCHEM LABORATORIES CO LTD (CN)
International Classes:
C07C1/28; C07C13/605
Domestic Patent References:
| WO2015089170A1 | 2015-06-18 |
Other References:
J BELZNER, BUNZ U, SEMMLER K, SZEIMIES G, OPITZ K, SCHLIITER A.-D, BELZNER, JOHANNES, BUNZ UWE, SEMMLER KLAUS, SZEIMIES GIINTER,: "Concerning the Synthesis of [l.l.l]Propellane", CHEMISCHE BERICHTE, VCH, DE, vol. 122, 19 September 1988 (1988-09-19), DE, pages 397 - 398, XP055767296, ISSN: 0009-2940
KLAUS SEMMLER, GUENTER SZEIMIES, JOHANNES BELZNER: "Tetracyclo[5.1.0.01,6.02,7]octane, a [1.1.1]propellane derivative, and a new route to the parent hydrocarbon", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, US, vol. 107, no. 22, 1 October 1985 (1985-10-01), US, pages 6410 - 6411, XP055378786, ISSN: 0002-7863, DOI: 10.1021/ja00308a053
REHM, J.D.DANIEL ET AL.: "A Facile Route to Bridgehead Disubstituted Bicyclo[1.1.1]pentanes Involving Palladium-Catalyzed Cross-Coupling Reactions", EUR. J. ORG. CHEM., vol. 107, 31 December 1999 (1999-12-31), XP55767298, DOI: 20200302193105Y
JIANG, JIAJUN: "Passage; Chemical Technology - Inorganic Part. Section 1-4. Industrial process", CHEMICAL TECHNOLOGY - INORGANIC PART, 30 April 1988 (1988-04-30), CN, pages 17 - 18, XP009532440, ISBN: 7-04-001004-6
STEPAN, A. F.SUBRAMANYAM, C.EFREMOV, I. V.DUTRA, J. K.O'SULLIVAN, T. J.DIRICO, K. J.MCDONALD, W. S.WON, A.DORFF, P.H.NOLAN, C. E., J. MED.CHEM., vol. 55, 2012, pages 3414
BURKHARD, J. A.GUEROT, C.KNUST, H.CARREIRA, E. M., ORG. LETT., 2012
WESTPHAL, M. V.WOLFSTADTER, B. T.PLANCHER, J.-M.GATFIELD, J.CARREIRA, E. M.: "10", CHEMMEDCHEM, 2015, pages 461 - 469
KOLB, HCFINN, MGSHARPLESS, KB, ANGEW. CHEM., INT. ED., vol. 40, 2001, pages 2004 - 2021
PATZEL, M.SANKTJOHANSER, M.DOSS, A.HENKLEIN, P., EUR. J. ORG. CHEM., 2004, pages 493
WASER, J.GASPAR, B.NAMBU, H.CARREIRA, E. M., J. AM. CHEM.SOC., vol. 128, 2006, pages 11693
BUNKER, K. D.SACH, N. WHUANG, Q.RICHARDSON, P. F., ORG. LETT., vol. 13, 2011, pages 4746
SPANGLER, JEZHU, H.ZHU, J.BARAN, PSJ, AM. CHEM. SOC., vol. 139, 2017, pages 3209
MAKAROV, ISBROCKLEHURST, CEKARAGHIOSOFF, K.KOCH, G.KNOCHEL, P, ANGEW. CHEM. INT. ED., vol. 56, 2017, pages 12774
JUNICHIRO KANAZAWAKATSUYA MAEDAMASANOBU UCHIYAMA, J. AM. CHEM. SOC, vol. 139, 2017, pages 17791
WIBERG,K.B.WALKER,F.H., JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 104, 1982, pages 523
WIBERG, KENNETH B.MCMURDIE, NEIL, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 113, no. 23, 1991, pages 8995 - 8996
ELLIOTT, LUKE D.KNOWLES, JONATHAN P.KOOVITS, PAUL J.MASKILL, KATIE G.RALPH, MICHAEL J.LEJEUNE, GUILLAUMEEDWARDS, LEE J.ROBINSON, R, CHEMISTRY-A EUROPEAN JOURNAL, vol. 20, no. 46, 2014, pages 15226 - 15232
REHM, J. D. DANIELZIEMER, BURGHARDSZEIMIES, GUENTER, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 9, 1999, pages 2079 - 2085
See also references of EP 3988520A4
KLAUS SEMMLER, GUENTER SZEIMIES, JOHANNES BELZNER: "Tetracyclo[5.1.0.01,6.02,7]octane, a [1.1.1]propellane derivative, and a new route to the parent hydrocarbon", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, US, vol. 107, no. 22, 1 October 1985 (1985-10-01), US, pages 6410 - 6411, XP055378786, ISSN: 0002-7863, DOI: 10.1021/ja00308a053
REHM, J.D.DANIEL ET AL.: "A Facile Route to Bridgehead Disubstituted Bicyclo[1.1.1]pentanes Involving Palladium-Catalyzed Cross-Coupling Reactions", EUR. J. ORG. CHEM., vol. 107, 31 December 1999 (1999-12-31), XP55767298, DOI: 20200302193105Y
JIANG, JIAJUN: "Passage; Chemical Technology - Inorganic Part. Section 1-4. Industrial process", CHEMICAL TECHNOLOGY - INORGANIC PART, 30 April 1988 (1988-04-30), CN, pages 17 - 18, XP009532440, ISBN: 7-04-001004-6
STEPAN, A. F.SUBRAMANYAM, C.EFREMOV, I. V.DUTRA, J. K.O'SULLIVAN, T. J.DIRICO, K. J.MCDONALD, W. S.WON, A.DORFF, P.H.NOLAN, C. E., J. MED.CHEM., vol. 55, 2012, pages 3414
BURKHARD, J. A.GUEROT, C.KNUST, H.CARREIRA, E. M., ORG. LETT., 2012
WESTPHAL, M. V.WOLFSTADTER, B. T.PLANCHER, J.-M.GATFIELD, J.CARREIRA, E. M.: "10", CHEMMEDCHEM, 2015, pages 461 - 469
KOLB, HCFINN, MGSHARPLESS, KB, ANGEW. CHEM., INT. ED., vol. 40, 2001, pages 2004 - 2021
PATZEL, M.SANKTJOHANSER, M.DOSS, A.HENKLEIN, P., EUR. J. ORG. CHEM., 2004, pages 493
WASER, J.GASPAR, B.NAMBU, H.CARREIRA, E. M., J. AM. CHEM.SOC., vol. 128, 2006, pages 11693
BUNKER, K. D.SACH, N. WHUANG, Q.RICHARDSON, P. F., ORG. LETT., vol. 13, 2011, pages 4746
SPANGLER, JEZHU, H.ZHU, J.BARAN, PSJ, AM. CHEM. SOC., vol. 139, 2017, pages 3209
MAKAROV, ISBROCKLEHURST, CEKARAGHIOSOFF, K.KOCH, G.KNOCHEL, P, ANGEW. CHEM. INT. ED., vol. 56, 2017, pages 12774
JUNICHIRO KANAZAWAKATSUYA MAEDAMASANOBU UCHIYAMA, J. AM. CHEM. SOC, vol. 139, 2017, pages 17791
WIBERG,K.B.WALKER,F.H., JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 104, 1982, pages 523
WIBERG, KENNETH B.MCMURDIE, NEIL, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 113, no. 23, 1991, pages 8995 - 8996
ELLIOTT, LUKE D.KNOWLES, JONATHAN P.KOOVITS, PAUL J.MASKILL, KATIE G.RALPH, MICHAEL J.LEJEUNE, GUILLAUMEEDWARDS, LEE J.ROBINSON, R, CHEMISTRY-A EUROPEAN JOURNAL, vol. 20, no. 46, 2014, pages 15226 - 15232
REHM, J. D. DANIELZIEMER, BURGHARDSZEIMIES, GUENTER, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, vol. 9, 1999, pages 2079 - 2085
See also references of EP 3988520A4
Attorney, Agent or Firm:
KANGXIN PARTNERS, P.C. (CN)
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