TFA, amides

A/-(Trifluoroacetyl)succinimide, THF or toluene, reflux, 86-99% yield. Phenols and amines react to give the phenolic ester and TFA amides respectively. ... 

TFA, Ph3P, NBS, CH2CI2, Pyr, 81-99% yield. This methodology can be used for the preparation of other amides from simple carboxylic acids. ... 

This group was developed for the protection of primary amides of amino acids. It is introduced by amide bond formation with the benzhydrylamine. It is cleaved with 1 MSiCl4/anisole/TFA/0° or 1 MTMSOTf/thioanisole/TFA, 0°. Cleavage occurs by initial sulfoxide reduction followed by acidolysis. ... 

The trityl group was introduced on a primary amide, RCONH2, in the presence of a secondary amide with TrOH, AC2O, H2SO4, AcOH, 60°, 75% yield. It is stable to BOC removal with 1 N HCl in 50% isopropyl alcohol, 30 min, 50°, but can be cleaved with TFA. The following table gives the cleavage rates with TFA for a number of protected primary amides. 

With monoamines, the oxazolones give the normal ring-opened products, A-TFA amino acid amides, but with aniline both forms... 

Cyclization of amide 312 by treatment with TFA gave 1 li-butyl-1,3, 4,6,7,1 l -hexahydro[l,4]oxazino[3,4-a]isoquinolin-4-one 313 (97JOC2080). 

Finally, we tried to deprotect the amide nitrogen of the obtained pyridi-nones upon reflirx in neat trifluoroacetic acid (TFA) for 18 h [ 116]. Products were isolated in 73% and 79% yield, respectively. In contrast, upon microwave irradiation at 120 °C for only 20 min, a (1 2) TFA/DCM mixture sufficed to deprotect the pyridinones (isolated yields 75% and 73% respectively). Surprisingly, deprotection with either refluxing neat TFA (18 h) or microwave irradiation in neat TFA with a catalytic amount of methanesulfonic acid (20 min) did not work for dihydrofuropyridinone. 

Scheme 3) [30]. The pY + 3 diversity alcohols (Ri)-OI I (Fig. 15) were attached to the template through a Mitsunobu coupling to provide ether derivatives of 16. Palladium-mediated Alloc deprotection followed by amide formation using the phosphate-ester-containing diversity acids (R2)-C02H provided the fully coupled resin-bound products of 17. Cleavage from the resin with 95% TFA/H20, which also afforded benzyl phosphate deprotection, followed by reversed-phase (RP) semipreparative... 

In an extension to the xanthenyl theme, the benzyl hydrogen was replaced with a substituted / -methoxyphenyl ring to give linker 35 (Scheme 10) [41]. Peptide amides were cleaved rapidly and in high purity with TFA-DCM (1 9) for 15 min or as a protected fragment with TFA-DCM (1 99) for 3-10 min. 

MAMP (Merrifield, Alpha-MethoxyPhenyl) resin 44 is an alternative to aldehyde linkers to construct TV-substituted amides [53], Nucleophilic displacement of the benzylic chloride with an amine followed by acylation yielded a secondary amide which was released upon a low ( 10%) concentration of TFA (Scheme 16). 

Further attempts to effect a one-step synthesis of the hasubanan skeleton via acid-catalyzed cyclization of urethane 28 and unsaturated amides 31 and 32 were explored, using trifluoroacetic acid (TFA) (Scheme 1). Treatment of... 

FIGURE 6.7 A HILIC column (Tosoh Amide-80, 25 cm x 4.6 mm, 5 lm particles) at different flow rates with a solvent of ACN/water/0.1%TFA. The gradient is 80% to 15% ACN. Protein standards A = aprotinin, B = cytochrome C, C = carbonic anhydrase. 

Reductive Amidation of Aldehydes. The reductive amidation of aldehydes using an organosilane as the reducing agent has been realized. Benzaldehyde reacts over a 74-hour period with triethylsilane and acetonitrile in 75% aqueous sulfuric acid at room temperature to produce an 80% isolated yield of N-benzylacetamide (Eq. 169).313 Octanal fails to react under the same conditions.313 Reductive amidation of aldehydes also occurs with the reagent combination Et3SiH/TFA/primary amide (Eq. 170).326... 

An intramolecular Heck cyclization strategy was developed for the construction of indole and benzofuran rings on solid support [82], enabling rapid generation of small-molecular libraries by simultaneous parallel or combinatorial synthesis. Sn2 displacement of resin-bound y-bromocrotonyl amide 97 with o-iodophenol 96 afforded the cyclization precursor 98. A subsequent intramolecular Heck reaction using Jeffery s ligand-free conditions furnished, after double bond tautomerization, the resin-bound benzofurans, which were then cleaved with 30% TFA in CH2CI2 to deliver the desired benzofuran derivatives 99 in excellent yields and purity. 

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