Trifluoroacetic acid deprotection

Trifluoroacetic acid deprotection. Trialkylsilanes in combination with an acid as a hydride donor are useful for ionic hydrogenation. DuPont chemists recommend triethyl- or triisopropylsilane as scavengers for carbocationic by-products formed in TFA deprotection of amino acids. In fact, triethylsilane can be more effective than ethanedithiol, a commonly used scavenger. 

The anthranilic acid derivatives 227 were reacted with /i t7-butyl chlorosulfonylcarbamate <2002BMC1509> in pyridine to afford sulfamides 228. Conversion of the latter to the corresponding benzothiadiazin-4-ones 229 was effected by trifluoroacetic acid deprotection followed by cyclization with ethanolic sodium ethoxide (Scheme 27) <2003BMC367>. 

Regeneration of the parent carbonyl compound from tosylhydrazones and 2,4-dinitrophenylhydrazones can be carried out in high yield using sodium nitrite in trifluoroacetic acid. Deprotection of tosylhydrazones using thallium triacetate in acetic add is also elficient. Oximes yield the carbonyl product on treatment with bromine in aqueous sodium bicarbonate, and the same conditions can be used to hydrolyse tosylhydrazones if HMPA is present. Aqueous nitric acid was found to be superior to both sulphuric and hydrochloric adds for the cleavage of the hydrazones (90) to the corresponding cyclohexanones. ... 

Smith, Kline and French researchers elected to synthesize SKF 73678 (548) in an entirely different way (DeMartinis et al., 1976). rm-Butyl ester 544, a result of 7-aminocephalosporanic acid derivatization, condensed with benzaldehyde to give imine 545. Methylthiolation, followed by exchange of methoxy for methylthio (546) gave 7a-methoxyamine rm-butyl ester (547). Acylation with trifluoromethylthioacetic acid and DCC, followed by trifluoroacetic acid deprotection produced 548. 

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain pro-teaing groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N -deprotection. Only /ert-butyl esters and carbamates ( = Boc) are solvolyzed in this mixture. 

The cleavage of this group proceeds by initial reduction of the sulfoxide, which then makes the resulting methylthiobenzyl ether labile to trifluoroacetic acid. Thus, any method used to reduce a sulfoxide could be used to activate this group for deprotection. 

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. 

THF) containing 10% (v/v) of trifluoroacetic acid (TFA). After microwave irradiation for 25 s at 60 °C, the mixture was concentrated to dryness, 5 equivalents each of N,N-diisopropylethy]amine (DIEA) and (S)-proline acid chloride in bdmimPF6/ THF were added, and the resulting mixture was stirred at room temperature for 3 min. Finally, after in situ deprotection with 20% piperidine (v/v) in bdmimPF6/ THF at 60 °C for 1 min in the microwave reactor, the target compounds were obtained as mixtures of diastereomers. 

Furthermore, multicomponent reactions can also be performed under fluorous-phase conditions, as shown for the Ugi four-component reaction [96], To improve the efficiency of a recently reported Ugi/de-Boc/cyclization strategy, Zhang and Tempest introduced a fluorous Boc group for amine protection and carried out the Ugi multicomponent condensation under microwave irradiation (Scheme 7.84). The desired fluorous condensation products were easily separated by fluorous solid-phase extraction (F-SPE) and deprotected by treatment with trifluoroacetic acid/tet-rahydrofuran under microwave irradiation. The resulting quinoxalinones were purified by a second F-SPE to furnish the products in excellent purity. This methodology was also applied in a benzimidazole synthesis, employing benzoic acid as a substrate. 

This approach may find application in peptide bond formation that would eliminate the use of irritating and corrosive chemicals such as trifluoroacetic acid and piperidine as has been demonstrated recently for the deprotection of N-boc groups (Scheme 6.7) a solvent-free deprotection of N-tert-butoxycarbonyl group occurs upon exposure to microwave irradiation in the presence of neutral alumina doped with aluminum chloride (Scheme 6.7) [41]. 

M[pz(A4)] A = S2ML2. The octakis(.V-R)porphyra/,ines reported by Schramm and Hoffman (2), M[pz(S-R)8 (M = Ni, Cu), (60), can be converted to the octathiolate M[pz(S )g] (Scheme 11) via reductive cleavage of the sulfur-carbon bond when R = benzyl (Bn), and this tetra-bis(dithiolate) can then be peripherally capped with metal-ligand systems to yield peripherally tetrametalated star porphyrazines. The benzyl dinitrile 57 can be macrocyclized around magnesium butoxide to form [Mg[pz(S-Bn)8] (58) (35-40%), which can then be demetalated with trifluoroacetic acid to form 59 (90%), which is subsequently remetalated with nickel or copper acetate to form 60a (95%) and 60b (70%) (Scheme 11) (3, 23, 24). Deprotection of 60a or 60b with sodium in ammonia yields the Ni or Cu tetra-enedithiolates, 61a or 61b to which addition of di-ferf-butyl or n-butyl tin dinitrate produces the peripherally metalated star porphyrazines 62a (37%), 62b (80%), and 62c (41%). 

Deprotection 2.1 mg Fmoc-Arg(Pbf)-OH (Merck Schuardt OHG) was dissolved in 1 ml acetonitrile (99.5%, CALEDON) in a 50 ml flask attached to a well-regulated supply of nitrogen (at 5 psi) and equipped with a septum and PEEK tubing leading to the mass spectrometer. 4 ml of trifluoroacetic acid (99.9%, CALEDON) was injected in the reaction flask. 

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