Benzyl N‐[(Benzyloxy)methyl]carbamate: An Improved Aminomethylation Electrophile for the Synthesis of (Benzyloxy)carbonyl (Cbz)‐Protected Chiral β2‐Amino Acids |
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Authors: | Cara E Brocklehurst Markus Furegati J Constanze D Müller‐Hartwieg Flavio Ossola Luigi La Vecchia |
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Institution: | 1. Preparation Laboratories, Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Klybeckstrasse 141, CH‐4057 Basel, (phone: +41?61?6964576;2. fax: +41?61?6968016) |
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Abstract: | α‐Aminomethylation of (R)‐DIOZ‐alkylated (DIOZ=4‐isopropyl‐5,5‐diphenyloxazolidin‐2‐one) substrates is a key step in the asymmetric synthesis of β2‐amino acids, but it is unfortunately often accompanied by formation of transcarbamation by‐products. Aminomethylation was tested using a range of electrophiles, and the amount of by‐product formation was assessed in each case. Benzyl N‐(benzyloxy)methyl]carbamate electrophile 3d is unable to form this by‐product due to its inherent benzyl substitution. Use of electrophile 3d showed an improved impurity profile in aminomethylation, thus leading to easier intermediate purification. |
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Keywords: | α ‐Aminomethylation Amino acids Transcarbamation Asymmetric synthesis |
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