Amino alcohols Benzyl isocyanate

Amino alcohols Azidotrimethylsilane, 24 Benzyl isocyanate, 30 Diethylamine, 312 Morpholine, 14 Pyrrolidine, 14... 

The first step in the overall synthetic scheme (Scheme 6) is the condensation of an appropriate carboxylic acid with trifluoroacetaldehyde. The carboxylic acid is chosen to impart specificity for the target enzyme. In one example,[28 the dianion of cyclohexanepropanoic acid (29) was formed by the addition of LDA and then quickly condensed with trifluoroacetaldehyde to form the p-hydroxy acid 30 as a racemic mixture of erythro- and threo-isomers. The p-hydroxy acid 30 is then protected with TBDMSOTf forming 31. Diphenyl phosphorazidate, TEA, and benzyl alcohol were then utilized in a Curtius rearrangement of the protected alcohol 31, which proceeds through an isocyanate intermediate that yields the protected amino alcohol 32 upon reaction with benzyl alcohol. In order for this step to occur at an appreciable rate, a second equivalent of triethylamine had to be added. The amino alcohol 32 was then deprotected and coupled with Boc-Phe-Leu-OH to give the trifluoromethyl alcohol 33, which was oxidized to the corresponding trifluoromethyl ketone 34 as a 1 1.2 mixture of diastereomers using the Dess-Martin periodinane procedure. Thus far, the compound shown in Scheme 6 is the only compound that has been synthesized by this method, but it is reasonable to assume that many other similar fluoro ketones can be produced by this scheme. 

A soln. of benzyloxycarbonyl isocyanate in dry dichloromethane added dropwise over 30 min under N2 to a vigorously stirred soln. of benzyl alcohol in the same solvent at 0°, stirred for 1 h at the same temp., and then at room temp, overnight - product. Y 99%. The formed imides are potential Gabriel amino group synthons. F.e. and preferential N-decarbalkoxylation s. L. Grehn, U. Ragnarsson et al., Synthesis 1988, 992-5. 

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