| Modified Michaelis-Arbusov Reaction for Phosphonate Formation |
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Dr Will Watson
During the synthesis of a Cathepsin S inhibitor workers at Boehringer Ingelheim had problems converting the alcohol shown above to the phosphonate. Conversion of the alcohol to a chloride followed by traditional Michaelis-Arbusov reaction was unsatisfactory as the chloride was unstable.
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| N-Acetyl Enamide Synthesis |
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Dr Will Watson
Workers at Boehringer Ingelheim have recently published a simple, practical, and scaleable method for preparing N-acetyl enamides. The method is based on a literature method where ketoximes are reductively acetylated with iron powder and acetic anhydride.
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| 3-Methylindole Synthesis |
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Dr Will Watson
Workers at Merck have recently published a new synthesis of 3-methylindoles. N-Boc-allyl amine and an ortho-chloroaryl triflate are coupled together in a 3-step one pot approach. The first step is a Heck reaction catalysed by Pd(OAc)2 with dppf as ligand and NaOAc in acetonitrile.
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| Mild Deprotection of TBDMS Ethers |
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Dr Will Watson
RO-TBDMS → ROH
TBDMS ethers are very useful protecting groups in organic synthesis and there are already many methods for their removal, but this latest deprotection method is particularly mild.
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| Use of Organozinc Reagents |
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Dr Trevor Laird
Did you realise that over 60% of the papers on organozinc reagents use diethyl zinc as the reagent? The reason is that it is cheap, readily available on scale and, most importantly, is free from metal salts which can affect the progress of many reactions.
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| Synthetic Challenges |
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Dr Trevor Laird
Here are some recent examples of drugs in Phase II, published in C & E News (April 12, 2010) and taken from an ACS meeting. The Pfizer drug SAM-531 looks fairly straightforward to make, but AZD2624, MK-4305, PF-04629991 and particularly BMS-650032 are possibly more challenging.
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Introduction of Fluorine into Organic Molecules
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Dr Trevor Laird
Two interesting papers in Angewandte Chemie International Edition (Yamada S et al, pp2215-8, and Anbarasan P et al pp 2219-2222) describe ways of introducing F into a specific position in an aromatic or heteroaromatic structure.
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Unusual Method of Making 4-Aminoquinolines
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Dr Trevor Laird
The thermolysis of N-aryl-pyrazoles with a carboxyate substituent leads via decarboxylation to N-heterocyclic carbenes, which rearrange to the aminoquinolines, via a ring-opening ring-closing mechanism ( Schmidt A et al, Angew Chem Int Ed, 2010,49,2790-2793).
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Asymmetric Phase Transfer Catalysis
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Dr Trevor Laird
Asymmetric PTCs can be made by alkylation of commercially available alkaloids such as quinine and cinchonidine. However, commercially available cinchonidine often contains up to 10% of dihydrocinchonidine, which will also alkylate to give a mixture of cinchonidinium and dihydrocinchonidinium salts which are hard to separate.
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| ... and finally - you might be an engineer if...... |
| ... ... .. in college you thought Spring Break was metal fatigue failure. |
