Tetramethyluronium chloride hexafluorophosphate

The salt is prepared by reaction of hydroxybenzo-triazole with tetramethyluronium chloride hexafluorophosphate. 

For both the preliminary and fined test peptides, it was necessary to prepare all possible isomers as standards for analysis. These reference peptides were synthesized using a PE-ABD 430A peptide synthesizer configured for FastMoc synthesis protocols. Piperidine (20%) in N-methylpyrrolidone (NMP) was used to deprotect the N-terminal amino acid. To activate each amino acid in the reaction vessel, the following was used 1.0 mM amino acid, 1.0 mM 2-(lH-benzotriazol-l-yl)-l-l-2,3, tetramethyluronium hexafluorophosphate (HBTU) in 1 M 1-hydroxybenzotriazole (HOBT) in NMP, 2.0 mM diisopropylethylamine (DIEA). Each His residue was double-coupled. HBTU, DIEA, piperidine, DMF and NMP were purchased from ABI. Methylene chloride was purchased from Burdick and Jackson. 

Another potential problem with DCC is that at the completion of the reaction some DCU remains in solution with the product, necessitating additional purification. Water-soluble carbodiimide derivatives such as l-Cyclohexyl-3-(2-morpholinoethyl)carbodiimide Metho-p-toluenesulffonate and l-Ethyl-3-(3 -dimethylaminopropyl)carbodiimide Hydrochloride (EDCI) obviate this problem, as they are removed by a simple extraction. Many newer coupling agents have been developed for peptide synthesis and other acylation reactions. These include Benzotriazol-l-yloxytris(dimethylamino)phosphonium Hexafluorophosphate (BOP)," 0-Benzotriazol-l-yl-N,N,N, N -tetramethyluronium Hexafluorophosphate (HBTU)," Bis(2-oxo-3-oxazolidinyl)phosphinic Chloride (BOP-Cl), and (1 //-1,2,3-benzotriazol-1 -yloxy)tris(pyrTolidino)phosphonium hexafluorophosphate (PyBOP). In addition to linear and polymeric amides, lactams of various ring sizes have been synthesized using these methods (eq 1)."... 

A second peptide coupling reagent that incorporates the HOBT unit is 0-Benzotriazol-I-yl-N,N,N, N -tetramethyluronium Hexafluorophosphate (HBTU), which can be prepared by the reaction of tetramethylurea with oxalyl chloride followed by treatment with HOBT and Potassium Hext uorophosphate. HBTU can then be used as a direct coupling agent as outlined in eq 7. 

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