Hexafluorophosphate esterification

With the aid of BOP [benzotriazol-l-yl-oxytris(dimethylamino) phosphonium hexafluorophosphate, Castro s reagent]20 in the presence of DMAP it is possible to transform the free carboxylic acid 33 into activated intermediate 34 in preparation for subsequent esterification with 14 Other methods for esterification include application of DCC and the procedures introduced by Yamaguchi and Mukaijama (see Chapters 5, 6, and 9). 

In most of their reactions, the pyridine- and azinecarboxylic acids and their derivatives behave as any other acid (cf. Scheme 86). However, some acid chlorides can be obtained only as hydrochlorides, and we must also consider decarboxylation. Esterification of pyridine carboxylic acids can be usefully achieved via in situ generation of the acid fluoride. For example, treatment of picolinic acid with a stoichiometric amount of N,N,N,A-tetramethylfluoroformami-dinium hexafluorophosphate (TFFH) in dichloromethane and triethylamine leads to generation of the acid fluoride, which reacts with (3-methyloxetan-3-yl)methanol to give the corresponding ester in 95% yield <2004S2485>. 

Smooth esterification of 5-hydroxymethylpyrazol-3-one 71 was possible with A -Zcrt-butoxycarbonyl glycine 72 in 1,2-dichloromethane in the presence of DMAP and DCC to yield pyrazol-3-one ester 73 (02EJP121) (Scheme 18). Compound 71 was also esterified with 2-(6-methoxy-2-naphthyl)propionic acid 74 in DMF and in the presence of CDI to give pyrazol-3-one ester 75. Coupling of 5-aminomethylpyrazol-3-one hydrochloride 76 with trityloxyacetic acid 77 in DMF containing triethylamine and (benzotriazol-l-yloxy)trw(dimethylamino) phosphonium hexafluorophosphate (BOP) afforded pyrazol-3-one amide 78. 

The extent of interaction between the anion and cation in the IL has also been shown to affect the esterification reaction. Highly coordinating anions [e.g. trifluoroacetate and tetrafluoroborate), which have strong interactions with the cation, result in lower yields than anions with weaker interactions e.g. triflate and hexafluorophosphate). The more highly coordinating anions are expected to have a larger barrier for the formation of an encounter complex between the cation and the carbojq lic acid reactant, thus raising the barrier for acid catalysis. 

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