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9th June 2010 @ 03:48
Preparation of starting material for the [url=http://www.thesynapticleap.org/node/317]Ugi reaction[/url] [data=size:500x150]174[/data] [data=size:500x180]176[/data] [b]Hazard and Risk Assessment:[/b] Reaction Class: 2 Hazards: T Toxic, X Irritant, C Corrosive Risk rating: U = Unlikely Start time: 11:05 AM 09/06/2010 End time: 10:45 AM 10/06/2010 To a mixture of phenethylamine (1.00 g, 8.25 mmol), benzyltriethylammonium chloride (TEBACl) (94 mg, 413 µmol, 5 mol%) and NaOH (1.32 g, 33.0 mmol, 4 eq.) in DCM (20 mL) was added chloroform (1.48 g, 1.0 mL, 12.4 mmol, 1.5 eq.) and heated to reflux. - after 12 h the solution was cooled to room temperature and stirred vigorously for another 12 h. 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, 4:1, stain: KMnO4), Rf = 0.50 (fast elution), TLC (hexane:EA, 4:1, stain: KMnO4). [b]Result:[/b] Product [b]MW34-1[/b]: 633 mg (4.82 mmol, 58%) brown liquid, pungent smell; reference yield : 60% [1] This patented procedure offers a convenient access for the synthesis of 2-Phenylethyl isocyanide in 1 step. Compound also commercially available --> upscale reaction [url=http://www.ourexperiment.org/racemic_pzq/338][b]MW34-2[/b][/url] See also: [url=http://www.ourexperiment.org/racemic_pzq/1564]Preparation of 2-phenylethyl isocyanide - alternative route (MW34-3)[/url] [b]Analytical data:[/b] Rf (hexane:EA, 4:1) = 0.50. [url=http://www.ourexperiment.org/data/182.html]1H NMR[/url] (CDCl3, 200 MHz): δ = 2.95-3.02 (m, 2H), 3.57-3.65 (m, 2H), 7.21-7.39 (m, 5 H). [url=http://www.ourexperiment.org/data/188.html]13C NMR[/url] (CDCl3, 50.3 MHz): δ = 35.6, 42.9, 127.2, 128.7 (2C), 128.7 (2C), 136.7, 156.6. [url=http://www.ourexperiment.org/data/192.html]IR[/url] (neat): nu =3031 cm-1, 2147, 1454, 746, 697, 577, 496. C9H9N (131.2). [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/jm801529c][2] "Synthesis, Biological Evaluation, and Molecular Docking of Ugi Products Containing a Zinc-Chelating Moiety as Novel Inhibitors of Histone Deacetylases", A. Grolla, V. Podesta`, M. G. Chini, S. Di Micco, A. Vallario, A Genazzani, P. L. Canonico, G. Bifulco, G. C. Tron, G. Sorba and T. Pirali, [i]J. Med. Chem.[/i] [b]2009[/b], [i]52[/i], 2776–2785.[/url]
Attached Files
Reaction Scheme
Table1
1H NMR MW34-1
1H NMR MW34-1 JCAMP-DX
IR MW34-1
13C NMR MW34-1
13C NMR MW34-1 JCAMP-DX
IR MW34-1