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3571609Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37)
Experiments
profiles.google.com-micha.wolfleMichael Wolfle upscale reaction -->[url=http://www.ourexperiment.org/racemic_pzq/386] starting material for reaction[b] MW40[/b] [/url] [*] Alternative procedure:[url=http://www.ourexperiment.org/racemic_pzq/1587]Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)[/url] [b]References:[/b] [url=http://v3.espacenet.com/publicationDetails/biblio?CC=WO&NR=2009115333A1&KC=A1&FT=D&date=20090924&DB=EPODOC&locale=en_ep][1] “Novel Synthesis of Praziquantel“, A. Dömling,[i] Patent Application[/i] [b]2009[/b], WO 2009/11533(A1), Language: German.[/url] [url=http://dx.doi.org/10.1021/jo047924f][2] "Microwave-Assisted Synthesis of Isonitriles: A General Simple Methodology" A. Porcheddu, G. Giacomelli and M. Salaris, [i]J. Org. Chem.[/i] [b]2005[/b], [i]70[/i], 6, 2361–2363, DOI: 10.1021/jo047924f.[/url] [b]Analytical data:[/b] (from reference [2]) [b]8:[/b] IR: (neat) 2999, 2924, 2850, 2147, 1674, 1590, 1516, 1261, 1025. 1H NMR (CDCl3): delta (ppm) 6.72 (m, 3H), 3.84 (s, 6H), 3.63 (t, J = 7 Hz, 2H), 2.71 (t, J = 7 Hz, 2H). 13C NMR (CDCl3): delta (ppm) 156.5, 150.1, 146.5, 132.9, 122.2, 115.7, 113.1, 56.8, 56.1, 45.7, 37.1. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C, 69.01; H, 6.89; N, 7.24.]]>Ugi reaction – (MeO)2-derivative of PZQ

Reaction Scheme


Table1


Hazard and Risk Assessment:
Reaction Class: 2
Hazards: T Toxic, X Irritant, C Corrosive
Risk rating: U = Unlikely

Start time: 4:50 PM 17/06/2010
End time: 11:07 AM 21/06/2010

To a mixture of 3,4-dimethoxyphenethylamine (1.00 g, 5.52 mmol), benzyltriethylammonium chloride (TEBACl) (64 mg, 276 µmol, 5 mol%) and NaOH (442 mg, 11.0 mmol, 2 eq.) in CH2Cl2 (20 mL) was added chloroform (1.0 g, 0.67 mL, 8.79 mmol, 1.5 eq.) and heated to reflux. After 1 h added more NaOH (442 mg, 11.0 mmol, 2 eq.) – two equivalents of NaOH could be too less, see result MW37-2
- after 12 h the solution was cooled to room temperature and stirred vigorously for 3 d.
TLC (hexane:EA, 3:1, stain: KMnO4) – some side products, starting material?

Work-up: quenched with water, extracted with DCM, washed with 1 N aq. HCl-solution, dried over magnesium sulfate, concentrated.
- dark brown oil
- purification by column chromatography (silica gel, hexane/EA, 3:1, stain: KMnO4, Rf = 0.25)

Result:
Product MW37-1: 525 mg (2.75 mmol, 50%) brown liquid

Analytical data:[2]
Rf (hexane:EA, 3:1) = 0.25.
1H NMR (CDCl3, 200 MHz): δ = 2.92 (t, J=6.9 Hz, 2H), 3.58 (t, J=6.9 Hz, 2H), 3.86 (s, 3H), 3.88 (s, 3H), 6.75-6.86 (m, 3 H).
IR (neat): nu = 3004 cm-1, 2939, 2836, 2147, 1592, 1515, 1454, 1260, 1236, 1140, 1024, 802, 762.
MS (APCI (+)) m/z (%): 192 (100) [M]+.
HRMS (ESI (+)) Calcd. for [C33H40N3O6]+ (for [M3H]+): 574.2912, found: 574.2914.
C11H14NO2 (192.2).

Convenient one-step synthesis to the isocyanide MW37
--> upscale reaction
--> starting material for reaction MW40
  • Alternative procedure:Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)

    References:
  • [1] “Novel Synthesis of Praziquantel“, A. Dömling, Patent Application 2009, WO 2009/11533(A1), Language: German.

    [2] "Microwave-Assisted Synthesis of Isonitriles: A General Simple Methodology" A. Porcheddu, G. Giacomelli and M. Salaris, J. Org. Chem. 2005, 70, 6, 2361–2363, DOI: 10.1021/jo047924f.

    Analytical data: (from reference [2])
    8:
    IR: (neat) 2999, 2924, 2850, 2147, 1674, 1590, 1516, 1261, 1025.
    1H NMR (CDCl3): delta (ppm) 6.72 (m, 3H), 3.84 (s, 6H), 3.63 (t, J = 7 Hz, 2H), 2.71 (t, J = 7 Hz, 2H).
    13C NMR (CDCl3): delta (ppm) 156.5, 150.1, 146.5, 132.9, 122.2, 115.7, 113.1, 56.8, 56.1, 45.7, 37.1.
    Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32.
    Found: C, 69.01; H, 6.89; N, 7.24.
    Linked Posts
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    3577219Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37)
    Experiments
    profiles.google.com-micha.wolfleMichael Wolfle upscale reaction -->[url=http://www.ourexperiment.org/racemic_pzq/386] starting material for reaction[b] MW40[/b] [/url] [*] Alternative procedure:[url=http://www.ourexperiment.org/racemic_pzq/1587]Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)[/url] [b]References:[/b] [url=http://v3.espacenet.com/publicationDetails/biblio?CC=WO&NR=2009115333A1&KC=A1&FT=D&date=20090924&DB=EPODOC&locale=en_ep][1] “Novel Synthesis of Praziquantel“, A. Dömling,[i] Patent Application[/i] [b]2009[/b], WO 2009/11533(A1), Language: German.[/url] [url=http://dx.doi.org/10.1021/jo047924f][2] "Microwave-Assisted Synthesis of Isonitriles: A General Simple Methodology" A. Porcheddu, G. Giacomelli and M. Salaris, [i]J. Org. Chem.[/i] [b]2005[/b], [i]70[/i], 6, 2361–2363, DOI: 10.1021/jo047924f.[/url] [b]Analytical data:[/b] (from reference [2]) [b]8:[/b] IR: (neat) 2999, 2924, 2850, 2147, 1674, 1590, 1516, 1261, 1025. 1H NMR (CDCl3): delta (ppm) 6.72 (m, 3H), 3.84 (s, 6H), 3.63 (t, J = 7 Hz, 2H), 2.71 (t, J = 7 Hz, 2H). 13C NMR (CDCl3): delta (ppm) 156.5, 150.1, 146.5, 132.9, 122.2, 115.7, 113.1, 56.8, 56.1, 45.7, 37.1. Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C, 69.01; H, 6.89; N, 7.24.]]>Ugi reaction – (MeO)2-derivative of PZQ

    Reaction Scheme


    Table1


    Hazard and Risk Assessment:
    Reaction Class: 2
    Hazards: T Toxic, X Irritant, C Corrosive
    Risk rating: U = Unlikely

    Start time: 4:50 PM 17/06/2010
    End time: 11:07 AM 21/06/2010

    To a mixture of 3,4-dimethoxyphenethylamine (1.00 g, 5.52 mmol), benzyltriethylammonium chloride (TEBACl) (64 mg, 276 µmol, 5 mol%) and NaOH (442 mg, 11.0 mmol, 2 eq.) in CH2Cl2 (20 mL) was added chloroform (1.0 g, 0.67 mL, 8.79 mmol, 1.5 eq.) and heated to reflux. After 1 h added more NaOH (442 mg, 11.0 mmol, 2 eq.) – two equivalents of NaOH could be too less, see result MW37-2
    - after 12 h the solution was cooled to room temperature and stirred vigorously for 3 d.
    TLC (hexane:EA, 3:1, stain: KMnO4) – some side products, starting material?

    Work-up: quenched with water, extracted with DCM, washed with 1 N aq. HCl-solution, dried over magnesium sulfate, concentrated.
    - dark brown oil
    - purification by column chromatography (silica gel, hexane/EA, 3:1, stain: KMnO4, Rf = 0.25)

    Result:
    Product MW37-1: 525 mg (2.75 mmol, 50%) brown liquid

    Analytical data:[2]
    Rf (hexane:EA, 3:1) = 0.25.
    1H NMR (CDCl3, 200 MHz): δ = 2.92 (t, J=6.9 Hz, 2H), 3.58 (t, J=6.9 Hz, 2H), 3.86 (s, 3H), 3.88 (s, 3H), 6.75-6.86 (m, 3 H).
    IR (neat): nu = 3004 cm-1, 2939, 2836, 2147, 1592, 1515, 1454, 1260, 1236, 1140, 1024, 802, 762.
    MS (APCI (+)) m/z (%): 192 (100) [M]+.
    HRMS (ESI (+)) Calcd. for [C33H40N3O6]+ (for [M3H]+): 574.2912, found: 574.2914.
    C11H14NO2 (192.2).

    Convenient one-step synthesis to the isocyanide MW37
    --> upscale reaction
    --> starting material for reaction MW40
  • Alternative procedure:Preparation of 2-(3,4-Dimethoxyphenyl)ethyl isocyanide (MW37-2)

    References:
  • [1] “Novel Synthesis of Praziquantel“, A. Dömling, Patent Application 2009, WO 2009/11533(A1), Language: German.

    [2] "Microwave-Assisted Synthesis of Isonitriles: A General Simple Methodology" A. Porcheddu, G. Giacomelli and M. Salaris, J. Org. Chem. 2005, 70, 6, 2361–2363, DOI: 10.1021/jo047924f.

    Analytical data: (from reference [2])
    8:
    IR: (neat) 2999, 2924, 2850, 2147, 1674, 1590, 1516, 1261, 1025.
    1H NMR (CDCl3): delta (ppm) 6.72 (m, 3H), 3.84 (s, 6H), 3.63 (t, J = 7 Hz, 2H), 2.71 (t, J = 7 Hz, 2H).
    13C NMR (CDCl3): delta (ppm) 156.5, 150.1, 146.5, 132.9, 122.2, 115.7, 113.1, 56.8, 56.1, 45.7, 37.1.
    Anal. Calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32.
    Found: C, 69.01; H, 6.89; N, 7.24.
    Linked Entries
    ]]>2010-06-17T06:55:28+00:002015-07-25T22:00:24+00:006https://www.ourexperiment.org/data/206.xmlhttps://www.ourexperiment.org/data/208.xmlhttps://www.ourexperiment.org/data/222.xmlhttps://www.ourexperiment.org/data/224.xmlhttp://www.ourexperiment.org/uri/42https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.htmlhttps://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.htmlhttps://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xmlhttps://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.pnghttps://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=357https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=358https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=359https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=360https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=377https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=378https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=379https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=380https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=381https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=391https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=461https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=462https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=463https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=1608https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=1609https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=7219https://www.ourexperiment.org/racemic_pzq/357/Preparation_of_234Dimethoxyphenylethyl_isocyanide_MW37.xml?revision=-1