• 10.1021/jo030360f
  • The Journal of Organic Chemistry
  • Volume 69
  • June 2004
  • pp 4361-4368

Adaptations Necessary to Improve Published Syntheses


This review addresses the published preparation of compound 10c as listed in JOC 69, 4361 (2004).  The stated preparation utilizes the inexpensive, commercially available diol, 6c.  The preparation begins by combining the diol with one equivalent of TESCl in the presence of excess base, namely triethylamine (TEA).  The ether was purified chromatographically (76%), and the unprotected alcohol was converted to the mesylate.  Upon treatment with NaN3 in DMF, a mixture of azido alcohol and azido Si ether were formed.  The Si ether was isolated chromatographically.  The azide was reduced with LAH to give the desired amino alcohol in poor overall yield.

In performing this synthesis, there were several troublesome features; namely, two chromatographies, the use of a protecting group with limited stability, the formation of a low molecular weight azide, and an LAH azide reduction forming a low molecular weight amino alcohol which was very difficult to isolate from the aluminum salts.  The following adaptations were made:

1)  No Si ether protection was done.  This was possible due to the fact that the diol was used in excess.  It is inexpensive and easily removed due to its water solubility.

2)  Using excess diol, the mono tosylate was formed in good yield under Schotten-Bauman conditions without chromatographic purification.

3)  The azide was formed and reduced in EtOH using catalytic hydrogenation to avoid the LAH reduction.  By employing EtOH as solvent, the azide was simply used directly in the reduction thereby avoiding the isolation of a high energy intermediate.

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