Trifluoroethanol from resin

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

After acid-free cleavage from the resin 120 with 1,1,1-trifluoroethanol in CH2CI2 and chromatographic purification, building blocks 162-165 are obtained in yields of 8-40%. Although the yields of the products 162 and 164 are enhanced compared to 163 and 165 (40% 8% and 17% 12%, respectively), a completely selective synthesis does not seem to be possible by this approach. An interesting feature here was the publication of an acid-free procedure for the cleavage of amines from trityl resins and a refinement of the Kaiser test. 

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