T-BOC derivative

Other reagents which have been found useful for the sjmthesis of t-BOC derivatives include the hazardous tert-butoxycarbonyl azide ... 

FIGURE 1.53 Cleavage of t-BOC derivative with trifluoroacetic acid. 

FIGURE 1.54 HPLC chromatogram of 2-amino-3-phenyl-l-propanol generated by cleavage of its t-BOC derivative with trifluoroacetic acid and clean-up on strata-X-C. 

FIGURE 3.2 Schedule followed in Perrin et al. [26]. Eleetrolyte 0.1 M phosphate buffer brought to the desired pH with TEOA injection 0.8 psi, 4 s Applied voltage 613 V/cm (amino aUcyl derivatives) or —490 V/cm (N-CBZ or N-t-Boc derivatives) Temperature 20 C Fused-silica capillary 40.8 cm x 50 p.m. (Reprinted from Perrin et al., J. Chwmatogr. A 2000, 883, 249-265. Copyright (2000). With permission from Elsevier.)... 

Indolizidines The t-Boc derivative of azacyclononene oxide is deprotonated at an cK-position of the epoxide ring by. r-RLi-TMEDA. A transannular reaction follows. 

A second nucleophilic catalyst supported by PtBS is the polymer-bound di-methylaminopyridine analog that was also used in latent biphasic catalysis with the poly(JV-alkylacrylamide) support 129 [131]. This example of a nucleophilic catalyst (133) was used to catalyze formation of a t-Boc derivative of 2,6-di-methylphenol (Eq. 70). In this case, the extent of recovery of the catalyst and the yields of product were directly comparable to those seen with thermomorphic systems. The isolated yield for the first five cycles of this reaction were 34.3, 60.9,82.2,94.6, and 99%. In this case we reused catalyst 133 through 20 cycles. Yields after the first few cycles were essentially quantitative (ca. 93% average for each of 20 cycles). Separation of the polymer from the aqueous ethanol phase was quantitative as judged by either visual observation or UV-visible spectroscopic analysis. 

Di-tert-butyl dicarbonate (or tert-butyl pyrocarbonate) t-Boc20 is an excellent reagent for the preparation of f-Boc-deriv-atives, N-silylmethylamines 128—132 (Table 24.6) (53,79). The stirring of a solution of (phthalimidomethyldimethylsilanyl) alkanols and hydrazine hydrate in absolute ethyl alcohol leads to the formation of aminomethyldimethylsilyl alcohols (53). Their purification on a chromatography column (silica gel) results in numerous degradation products. The protection of their amino groups with di-tert-butyl dicarbonate at room temperature affords more stable t-Boc-derivatives N-silylmethylamines 128-131 (Scheme 24.16). 

The /-butoxycarbonyl group (Boc, "t-box ) has been eMens vely used in peptide synthesis, and Boc derivatives of many amino acids are commercially available. The customary reagent for the preparation from the amine is t-butyl azidoformate in water, dioxane/water, DMSO, or DMF. The cleavage by acids of medium strength proceeds with concomitant loss of isobutene and carbon dioxide (L.A. Carpino, 1957, 1973 see section 4.1.2.2). 

M HCl, EtOAc, 25°, 30 min, 96% yield. With MeOH as the solvent, a diphenylmethyl ester is not affected. The combination of HCl/EtOAc leaves TBDMS and TBDPS ethers and t-butyl esters and nonphenolic ethers intact during BOC cleavage, but 5 -BOC derivatives are cleaved. 

The 1-Adoc group is very similar to the t-BOC group in its sensitivity to acid, but often provides more crystalline derivatives of amino acids. 

Problem 26.16 Show the mechanism for formation of a Boc derivative by reaction of an amino acid with di-fe/t-butyl dicarbonate. 

A versatile activating group for the removal of a-protons that are not benzylic is the carbamate fert-butoxycarbonyl, or t-Boc group, developed for this purpose by Beak and Lee in 1989. Its utility derives from the fact that the Boc group is easy to attach to a secondary amine, and easy to remove after a deprotonation/alkylation sequence. Moreover, stannylation affords a-amino-organostannanes that are themselves useful precursors of a-amino-organolithium compounds (Scheme 29) (see Section II). In a chiral pyrrolidine system, it has been shown that both deprotonation (H Li) and methylation (Li Me) occur with retention of configuration. 

Protection of pyrroles and indoles. These heterocycles undergo t-butoxycar-bonylation in 80-95% yield on reaction with 1 and a catalytic amount of DMAP in acetonitrile. The Boc group is cleaved almost instantaneously by TFA at 25°.1 The same conditions are useful for protection of the indole group of tryptophan.2 Primary amino acid esters can be converted into bis(Boc) derivatives, and amino groups of peptides also undergo t-butoxycarbonylation.3... 

In 1996, the tetraphenyl syn-bimane 1 (R = Ph) was obtained in 19% yield when the sodium salt of the 1,3,4-oxadiazinone 2 was treated with di-t-butyl dicarbonate in THF in an attempt to form the 3-Boc derivative. A mechanism was suggested for the conversion of 2 into syn-1 (R = Ph) which involved - ultimately - an intermediate of similar type to that which had been suggested previously for the transformation of 4-chloropyrazolin-5-ones into 1. 

The two commonest examples are the benzyl carbamates (CBZ derivatives) (4) and the t-butyl carbamates (BOC derivatives) (5) where the amino group is protected by the benzyloxycarbonyl or the t-butyloxycarbonyl groups respectively. 

Base, on the other hand, cannot touch the f-Boc group—the carbonyl group is too hindered to be attacked even by OH-, and t-Boc is strongly resistant to basic hydrolysis again, another example of an amide with an Achilles heel. The obvious way to make carbamates from amines is to react them with a carbamoyl chloride—this is how Z-groups are usually put on. Unfortunately, f-BuOCOCl is unstable, and we have to use some other electrophilic derivative—usually the anhydride B0C2O as here, for example. 

Hydrolysis of lactams. The N-Boc derivatives of lactams are hydrolyzed to Boc derivatives of w-amino acids by treatment with LiOH (3 equiv.) in aqueous THF at 25° in 85-95% yield. Treatment with NaOCH-, in t H,OH at 0° affords the esters of these products. The same reactions are useful for hvdrolysis or methanolysis of secondary amides. ... 

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