R-Butoxycarbonyl group

The t-butoxycarbonyl (rBoc) group is another valuable amino-protecting group. The removal in this case is done with an acid such as trifluoroacetic acid or /Moluenesulfonic acid.218 r-Butoxycarbonyl groups are introduced by reaction of amines with f-butoxypyrocarbonate or a mixed carbonate-imidate ester known as BOC-ON. 219... 

The sodium salt of diethyl N-(r-butoxycarbonyl)phosphoramidate (98) reacted with alkyl halides in boiling benzene in the presence of tetrabutylammonium bromide to give the corresponding N-alkyl derivatives (99) in 71-95% yields for primary alkyl halides and 38-58% yields for secondary a-halo esters (in MeCN). The phosphoryl and r-butoxycarbonyl groups were removed by treatment overnight with benzene saturated with dry HCl (Scheme 41). ... 

Catalytic hydrogenation of 2b yielded the tetrahydro derivative 68. One r-butoxycarbonyl group was removed selectively from the diesters (2c, 2d, and 2e) above 220°. Dimethyl acetylenedicarboxylate in boiling benzene converted 2b into the red Diels-Alder adduct 69a. This readily formed a dihydro derivative (69b), which lost ethylene above 220° to give 2f. 

Boc a r-butoxycarbonyl group (amino acid and peptide chemistry) (CH3)3C — O — C-... 

The previously known Inubushi syntheses of (4-)-isotetrandrine and ( —)-phaeanthine have now been adapted to preparations of (4-)-obaberine and (4-)-trilobine. ° Advantage was taken of the facts that (a) the r-butoxycarbonyl group is resistant to catalytic hydrogenation but is readily hydrolyzed, and (b) amides are readily formed from the reaction of an amine with a carboxylic ester of / -nitrophenol. The formation of the third diaryl ether bridge present in trilobine by reaction of the appropriate polyphenol with hot aqueous HBr had previously been carried out on other bisbenzylisoquinolines (see Schemes 5.4 and S.5) ... 

Amino acid protecting groups such as benzyloxycarbonyl and r-butoxycarbonyl groups are cleaved by BBr3. However, the hydrolysis of the ester function also occurs under the same reaction conditions. Debenzylation and debenzyloxymethylation of uracils proceed successfully in aromatic solvents, but demethyla-tion is more sluggish and less facile (eq 8). ... 

Kaiser and Muchowski (41) reduced A -(r-butoxycarbonyl) pyrroles to the corresponding pyrrolidines over 5% Pt-on-C at room temperature and atmospheric pressure. Under these conditions 0-benzyl groups are retained and 2,5-disubstituted pyrroles are reduced mainly or exclusively to thecis-2,5-disubstituted pyrrolidines. In some cases Pt-on-C proved superior to either Rh-on-C or PtO,. 

The fm-butoxycarbonyl group of 3-pyrrolylaminomethylenemalonate (1436, R = rBu) was converted into the carboxyl group (R = H) in 91% yield by the action of methanesulfonic acid at ambient temperature for 10 min (85JHC729). 

The procedure has been extended to the synthesis of 7V,7V -substituted diamines 166 from the diazides 164 and dichloroboranes 165177. Primary amines protected by the t-butoxycarbonyl group are obtained by the action of trialkylboranes R3B (R = Bu, s-Bu, CsHn or cyclohexyl) on the lithium or potassium salt of t-butyl 7V-(tosyloxy)carbamate (equation 62)178. 

Cleavage of carbamates. N-Benzyloxy- and N-r-butoxycarbonyl protected peptide derivatives can be selectively cleaved by reaction with ISilCHsls at 25-50° in the presence of side-chain blocking groups such as methyl esters or benzyl ethers. 

Protection of amino groups. The reagent (I) reacts with amino acid esters to give N-r-butoxycarbonyl (/-BOC) derivatives (2) in good yield. In a typical procedure glycine ethyl ester hydrochloride is suspended in chloroform and NaHCOj in water... 

Preparation of a-amino acid amides of aromatic amines (111) is easily conducted as a one-pot procedure by the modified Curtius reaction of aromatic carboxylic acids with DPPA, followed by reaction with iV-protected a-amino acids (equation 44). By this method, -t-butoxycarbonyl-L-leucine p-nitroanilide, which serves as a substrate for leucine aminopeptidase after deblocking of its r-butoxycar-bonyl group, has been efficiently prepared from p-nitrobenzoic acid and -r-butoxycarbonyl-L-leucine. 

Butanetetraol, 38 r-Butoxycarbonyl protecting groups, 47.417 p-r-Butylcalixarenes, 80 p-r-Butylphenol, 80... 

In fact, this case has been extensively studied and we consider it in more detail in Part B, Chapter 2. An example is the condensation of the enolate of a derivative of pyroglutamic acid and a protected form of glyceraldehyde. In the case of the (R)-aldehyde a single enantiomer is formed, whereas with the (5)-aldehyde a 1 1 mixture of two diastereomers is formed, along with a small amount of a third diastereomer2 The facial preference of the enolate is determined by the steric effect of the f-butoxycarbonyl group, whereas in the aldehyde the Felkin-Ahn TS prefers an approach anti to the a-oxygen. 

V-(r-Butoxycarbonyl)methanesulfonamide, MsNH N-Sulfonylcarbamates. Prepared by reaction ( butylchloroformate (EtyN-DMAP as base). As a nuci non, various alkyl groups can be attached to the nitr... 

Protecting-group manipulations. Tetrahydropyranyl ethers are switched to t-butyldimethylsilyl ethers on reaetion of RjSiOTf and EtjN in dichloromethane at room temperature. f-Butyl esters also undergo group exchange in the presence of t-butyl ethers. IV-r-Butoxycarbonyl derivatives of primary amines are further silylated with M SiOTf to give the base stable produets. Rapid acetylation of alcohols is promoted by the same catalyst. ... 

Pentafluorophenyl esters, obtained from pentafluorophenol and amino-acids protected with t-butoxycarbonyl groups, are formed without racemization of the amino-acid residue and are useful in peptide synthesis. Similarly useful is the fact that the pentafluorophenyl esters of JV-benzoxycarbonyl-y-methyl-L-glutamic acid and iV-benzoxycarbonyl-jS-methyl-L-aspartic acid show a particularly high ratio of the rate constants for coupling with L-valine methyl ester v. racemization in the presence of triethylamine. The reaction of S-(2,4-difluorophenyl)saIi( lic acid with alkyl chloroformates gives the esters (93 R = Et or Bu), which are claimed to... 

A related N-terminal-protecting group is r -butoxycarbonyl, abbreviated Boc ... 

Hydrogen bromide may be used to remove either the benzyloxycarbonyl or r r -butoxycarbonyl protecting group. The benzyloxycarbonyl protecting group may also be removed by catalytic hydrogenolysis. FMOC is removed in base. 

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