Author Topic: Experiments towards the Synthesis of Ergot Alka...  (Read 1309 times)

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Experiments towards the Synthesis of Ergot Alka...
« on: August 21, 2004, 09:22:00 AM »
Note ....I found this article to be of interest, I searched the Hive archives under 3 137 2002 and no bites. So with some hesitancy I bring this study to your attention although unable to secure the whole article I give you the bird eye view of it's content

Experiments Towards the Synthesis of the Ergot Alkaloids and Related Structures. Part 8.17 The Total Synthesis of 4-Methyl-2,3,4,4a,5,6-hexahydro-benzo[f]quinoline-2-carbonitrile Hydrochloride Hemihydrate, an Immediate Precursor of the Despyrrole Analogues of Lysergic Acid and Its Amides
Mark A.E. Bowman A1, Ralph E. Bowman A1, Roy V. Davies A2, Gerry Haran A2, Paul J. Harris A2, H. John Smith A1, Robert W. Steele A2, Nigel Walker A3, Keith Whiting A2

Journal of Enzyme Inhibition and Medicinal Chemistry Issue: Volume 17, Number 3,137-154,  2002
Publisher:Taylor & Francis Health Sciences, part of the Taylor & Francis Group

Exposure of the N-methoxycarbonyl-bicyclic-keto-acid 5 (improved preparation) to the Barnick g-keto-acid synthesis1 yielded an aqueous solution of the sodium salts of the g-keto-acids 26 and 27 which on heating at 60-65°C furnished the N-methoxycarbonyl-tricyclic-ketone 9 (55%) plus the hydroxy-ketone 28 which on acid treatment raised the yield of 9 to 68%. Reduction (NaBH4) of 9 yielded the alcohol 32 (94%) which was treated with thionyl chloride followed by copper (I) cyanide and sodium iodide in acetonitrile to give the tricyclic-N-methoxycarbonyl nitrile 35 whose relative configuration was obtained by X-ray analysis. Attempts to remove the N-methoxycarbonyl group from 35 were unsuccessful. Conversion of the alcohol 32 to its methoxypropyl ether 41 followed by reaction with ethereal MeLi-LiBr yielded the amino-alcohol 39 (75%) converted to the N-formyl-tricyclic alcohol 42 with formic-acetic anhydride (70%). The alcohol 42 was then converted into the N-formyl nitrile 44 via the chloride 43 as employed in the earlier synthesis of the nitrile 35. Removal of the N-formyl group from the nitrile 44 was achieved by refluxing methanolic hydrochloric acid to give the required amino-nitrile hydrochloride 46 (91%) whose structure was confirmed by X-ray analysis. Reaction of the free base with methyl iodide in ethyl acetate in the presence of calcium carbonate furnished the N-methyl base 48 isolated as its hydrochloride, hemihydrate 49 (59%). The overall yield of 49 via this eleven-step synthesis was 3.4%.



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« Reply #1 on: August 21, 2004, 10:56:00 AM »


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Methyl-hexahydro-benzoquinoline-2-carbonitrile ("N#CC3CN(C)C2CCC1=CC=CC=C1C2=C3")