T-butyl chloroformate

Protection of amino groups. Di-t.butyl dicarbonate called (Boc)20 (which is not made from the very unstable t.butyl chloroformate) is well known as the most popular reagent for the preparation of t.Boc protected amines, especially t.Boc-amino acids in peptide chemistry. 

Butyl chloroformate, 86, 1229 sec-Butyl chloroformate, 86 t-Butyl chloroformate, 40, 65, 86... 

Carboxylic, and arylsulfonic acid halides react rapidly with pyridines generating 1-acyl- and 1-arylsulfonylpyridinium salts in solution, and in suitable cases some of these can even be isolated as crystalline solids. The solutions, generally in excess pyridine, are commonly used for the preparation of esters and sulfonates from alcohols and of amides and sulfonamides from amines. 4-Dimethylaminopyridine (DMAP) is widely used (in catalytic quantities) to activate anhydrides in a similar manner. The salt derived from DMAP and t-butyl chloroformate is stable even in aqueous solution at room temperature. " ... 

Related Reagents. 7V-(r-Butoxycarbonyloxy)phthalimide N-(r-Butoxycarbonyloxy)succinimide t-Butyl Azidoformate t-Butyl Chloroformate Di-r-butyl Dicarbonate. 

Dione 21-Acetate To a stirred solution of 500 mg of 9o-fluoro-11(3,21-dihydroxy-16-methyl-1,4,16-pregnatriene-3,20-dione 21-acetate in 5 ml of benzene and 5 ml of chloroform are added 0.50 ml of t-butyl hydroperoxide and 0.1 ml of a 35% methanolic solution of benzyl-trimethyl ammonium hydroxide. After 18 hours at room temperature, water is added and the mixture thoroughly extracted with chloroform. The chloroform extract is washed with saturated aqueous sodium chloride and dried over magnesium sulfate. Evaporation of the Solvent and crystallization of the residue from acetone-ether gives Bo-fluoro-... 

In 2004, Alterman et al. apphed their cyanation protocol to the synthesis of N-(t-butyl)-3-(4-cyanobenzyl)-5-isobutylthiophene-2-sulfonamide [61]. Deprotection of the sulfonamide followed by carbamate formation via reaction with butyl chloroformate finally gave the target compoimd for biological evaluation as a selective angiotensin 11 AT2 receptor agonist (Scheme 65). The cyano derivative, however, showed only a low affinity for the AT2 receptor (Ki value >10 p,M). 

A number of other sulphoxide reduction reactions bear mentioning. The first, due to Marchelli and coworkers , is a very simple procedure whereby the sulphoxide is refluxed with t-butyl bromide and chloroform. A useful range of sulphoxides was studied and distillation of the reaction mixture (or percolation through a column of silica gel) gave pure sulphides in yields of > 90%. The procedure is appealing because of its experimental simplicity, and its use of a relatively inexpensive reagent. It may not be very successful with sterically hindered sulphoxides and the authors do not comment on this possibility. The mechanism of this reduction reaction is akin to that of BBrj (cf. Section II.A.3), except that the bromine trap is provided by a second mole of t-butyl bromide, as shown in equation (13) ... 

In this method, Furstner converts N-BOC protected pyrrole to the 2,5-dibromo compound (122) with NBS and this is followed by metalation and carbomethoxylation with t-butyl lithium in THF and subsequent trapping of the metalated species with methyl chloroformate to yield a pyrrole diester (123). Bromination of this diester at positions 3 and 4 with bromine in water followed by Suzuki cross-coupling with 3,4,5-trimethoxyphenyl boronic acid yields the symmetrical tetrasubstituted pyrrole (125). Base-mediated N-alkylation of this pyrrole with 4-methoxyphenethyl bromide produces the key Boger diester (126) and thereby constitutes a relay synthesis of permethyl storniamide A (120). 

In some reactions, the choice of PTC can actually alter the distribution of products for example, the reaction of t-butyl acrylate with chloroform under basic phase transfer conditions gives two major products, as illustrated in Scheme 5.8, the amounts of which are catalyst dependent [46],... 

Chloro-17-nitroso-3/i-hydroxy-5a-androstane 213, generated from the oxime 212 of epiandrosterone and t-butyl hypochlorite, reacts with cyclohexadiene in chloroform/metha-nol at — 20 °C to yield, after two weeks, epiandrosterone and the bridged dihydrooxazine 214 in an enantiomeric excess of better than 95%108. 

Alkanes pentane, hexane, heptane, cyclohexane Chlorinated solvents chloroform, dichloromethane, 1,2-dichloroethane Ethers diethyl ether, methyl-t-butyl ether, diisopropyl ether Esters ethyl acetate, butyl acetate Long-chain alcohols butanol, octanol Aromatics benzene, toluene, xylene Alkanes pentane, hexane, heptane, cyclohexane Diethyl ether... 

A tentative reservation exists about this work. As reported, in a communication, it as yet gives no explanation for the unexpected solubility of poly(r t-butyl isocyanide) in chloroform, nor does it describe a safeguard against the mutual solubility, i.e. plasticization, of polyisocyanides, which is a possibility between the non-crosslinked, otherwise insoluble support medium and the mobile solute. Yet, the rotation data is compelling. 

Method B. A solution of CTAP (2.02 g, 5 mmol) in t-butyl alcohol (20 ml) and water (5 ml) is added dropwise to a stirred solution of the alkene (5 mmol) in t-butyl alcohol (4 ml) at 20 °C, and stirring continued for 1-5 hours. Chloroform (50 ml) and 5 per cent aqueous sodium hydroxide solution (15 ml) are added, the mixture stirred for 30 minutes and the organic layer separated. The aqueous phase is extracted with chloroform (3 x 50 ml). The combined organic extracts are dried with magnesium sulphate, filtered, and evaporated to leave the w c-diol which is purified as in Method A. 

A close relative to Cbz is Boc (t-butyloxycarbonyl) that uses a different method to make esters easy to hydrolyse. It is added to an amine or an alcohol by the chloroformate 46 and, after the reaction, hydrolysed with acid—no water being needed. The ester is protonated and the t-butyl cation drops out in an Sn 1 reaction 49 to give the same intermediate 36 as in the removal of the Cbz group. 

Substituted (e.g. /7-methyl, p-t-butyl, p-chloro, and p-amino)benzoate esters of nortropine were synthesized14 by A-demethylation of the corresponding tropanyl esters with 2,2,2-trichloroethyl chloroformate. 

Scheme 5.8 Reaction of t-butyl acrylate with chloroform under basic phase transfer conditions...

At ambient temperature 3,3-dibromo-l,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (13.4 mmol) was dissolved in 100 ml apiece t-butyl alcohol and water followed by the dropwise addition of bromine (34.3 mmol) over 20 minutes. Thereafter 15 ml NaHC03 was added over 30 minutes to raise the pH to 6.5. A yellow solid formed and was removed. The filtrate was reduced to 100 ml, extracted twice with 50 ml chloroform, dried, concentrated, and the product isolated in 98% yield. H-NMR data supplied. 

To a suspension of p-t-butyl calix[4]arene (15.44 mmol) in 200ml DMF was added NaH (123.52 mmol) and 320ml DMF, the mixture stirred 1 hour, and N-(3-bromopropyl)phthalimide (123.52 mmol) added. The mixture stirred 7 days at ambient temperature, 100 ml water added, and the resulting precipitate collected. The precipitate was dissolved in 200 ml chloroform, washed with 50 ml 15% HCl, dried, and the product isolated in 54% yield, mp = 213-215 °C. MS and H-NMR data supplied. 

To 4-amino-1-benzylpiperidine (25 g) dissolved in 150 ml chloroform was added di-t-butyl dicarbonate (31.4 g) with ice cooling followed by stirring 2 hours at ambient temperature. The reaction mixture was diluted with chloroform, washed with water, dried, and concentrated. After recrystallizing from hexane/diisopropyl ether, 35.65 g of product was isolated. 

Acyl-, thioacyl- and imidoylcarbodiimides, having a C=X (X = O, S, or NR) adjacent to the cumulative bond are usually not stable at room temperature. However, sterically hindered N-functional carbodiimides with aliphatic t-butyl groups or aromatic 2,6-dimethylphenyl groups are often more stable, and they are generated in situ, for subsequent reactions. For example, N-alkyl substituted imidoylcarbodiimides, RN=C(Ph)N=C=NR are only stable as crystalline compounds for a short period of time. Even in chloroform solution they undergo subsequent reactions as indicated by the disappearance of the carbodiimide infrared band (see Table 5.1). ... 

Solubility An important consideration in the design of self-assembled structures is solubility. The cyanuric acid and melamine components are often poorly soluble in chloroform this insolubility hinders both synthesis and analysis of the self-assembled structure. We have often attached t-butyl benzyl, t-butyl phenyl, -Ci8H37, and eo-hexyl groups to provide sufficient CHCI3 solubility. 

Addition of aryl azides to CpRh(PMe3)(CNMe) resnlts in conpling of the aryl nitrene with the isocyanide to form (110) (Ar = Ph, p-tol) which can be converted to (111) (R = H, Me), another example of a carbene complex (see also 73, Section 2.4, Carbene Complexes) Replacement of COD in Rh2(COD)2(/u-Cl)(/u.-PBu 2) by t-butylisocyanide yields Rh2(CNBu04(M-Cl)(/r-PBu 2), which on treatment with one equivalent of lithium di(t-butyl)phosphide forms [Rh(CNBu )2(/x-PBu 2)]2, which has a planar Rh2P2 core and no Rh-Rh bond. In a chloroform solution, the last complex is slowly converted into a mixture of cis- and frani -[RhCl(CNBuO(/tr-PBu 2)]2, while oxidation with ferricinium hexafluorophosphate yields [Rh(CNBu )2(/u.-PBu 2)]2 - Both of the oxidized dimers contain Rh-Rh bonds. ... 

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