Formate 4-nitrophenyl-chloroformate

Eormation and subsequent cyclization of a hydroxyalkyl carbamate bearing an activating O-substituent can also be achieved in a one-pot procedure. When 2-(hydroxymethyl)aniline 394 was treated with -nitrophenyl chloroformate, the formation of the /)-nitrophenylcarbamate intermediate 395 was followed by in situ ring closure to give the 3,1-benzoxazin-2-one derivative efavirenz 250 in high yield and with high purity, free from the intermediate 395 (Scheme 74) <1998JOC8536>. 

Scheme 3.2.4 shows the synthetic route employed for the synthesis of linker-head intermediate 14 from half-sided Boc-protected amine 13 [28], via urea formation, mediated by 4-nitrophenyl chloroformate with 1-Cbz-piperazine, followed by hydrogenation of the Cbz group with palladium on carbon. 

Alternatively, Schultz and coworkers [59] have proposed an approach related to that of Burgess which utilizes azido 4-nitrophenyl carbamates 98 as activated monomers. Carbamates 98 were prepared in four steps from alcohol 95. Mesylation of 95 followed by azide displacement afforded the A-Boc-protected azide in high yield (80-90%). Boc deprotection and treatment of the resulting free amine with / -nitrophenyl chloroformate in the presence of pyridine in THF provided 98 (50-90% for the two steps). Solid-phase urea bond formation was performed on a Rink amide resin by coupling 98 (5 equiv.) in CH2CI2 in the presence of DIEA (7 equiv.) for 4 h at room temperature. Support-bound azide 99 was reduced in less than 2 h using... 

Kinetic studies on the reactions of X-phenyl chloroformates (52) with Y-pyridines in MeCN showed that the electron-rich formate moiety (O—C=0) overlaps with the pyridine tt-system, allowing rate-limiting formation of a tetrahedral intermediate. A similar conclusion was made following kinetic studies of the reactions of secondary alicyclic amines with phenyl (52 X = H) and 4-nitrophenyl chloroformate (52 X = 4-NO2) in aqueous solution, but the results for the aminolysis (anilines) of the same substrates in MeCN were considered to be more consistent with a concerted process. ... 

If, however, the /7-nitrophenyl ester of iV-henzoyl-L-leucine is treated with 1-methyl-piperidine in chloroform for 30 min and then coupled with glycine ethyl ester, the dipeptide isolated is almost completely racemic. Furthermore, treatment of the p-nitrophenyl ester of iV-benzoyl-L-leucine with 1-methylpiperidine alone leads to the formation of a crystalline material, C13H15NO2, having strong IR bands at 1832 and 1664 cm . Explain these observations, and suggest a reasonable stmcture for the crystalline product. 

Alcohols and phenols can be attached to support-bound alcohol linkers as carbonates [467,665,666], although few examples of this have been reported. For the preparation of carbonates, the support-bound alcohol needs to be converted into a reactive carbonic acid derivative by reaction with phosgene or a synthetic equivalent thereof, e.g. disuccinimidyl carbonate [665], carbonyl diimidazole [157], or 4-nitrophenyl chloro-formate [467] (see Section 14.7). The best results are usually obtained with support-bound chloroformates. The resulting intermediate is then treated with an alcohol and a base (DIPEA, DMAP, or DBU), which furnishes the unsymmetrical carbonate. Carbonates are generally more resistant towards nucleophilic cleavage than esters, but are less stable than carbamates. Aryl carbonates are easily cleaved by nucleophiles and are therefore of limited utility as linkers for phenols. 

Peptide synthesis, N-protection Acetic-formic anhydride. Adamantyl chloroformate. Benzylthiocarbonyl chloride. /-Butoxycarbonyl-N-hydroxysuccinimide ester. /-Butyl azido-formate. /-Butylcarbonic diethylphosphoric anhydride. /-Butyl fluoroformate. /-Butyl oxycarbonyl fluoride. /-Butyl pentachlorophenyl carbonate. /-Butyl 2,4,5-trichlorophenyl carbonate. Carbobenzoxy chloride. 3,5-Dimethoxybenzyl p-nitrophenyl carbonate. [2-(Diphenyl)isopropyljphenyl carbonate. /-Pentyl chloroformate. 

Enantiomerically pure dipeptide is obtained when the 4-nitrophenyl ester of N-benzoyl-L-leucine is coupled with ethyl glycinate in ethyl acetate. If, however, the leucine ester is treated with 1-methylpiperidine in chloroform for 30 min prior to coupling, the dipeptide in nearly completely racemized. Treatment of the leucine ester with 1-methylpiperidine leads to formation of a crystalline material of composition C13H15NO2, which has strong IR bands at 1832 and 1664 cm Explain how racemization occurs and suggest a reasonable structure for the crystalline material. 

The following chiral reagents were employed for diastereomer formation before sample application and chromatography on silica gel or silica gel G TLC plates (L)-leucine Af-carboxyanhydride for D,L-dopa-carboxyl- " C separated with ethyl acetate/formic acid/water (60 5 35) mobile phase and detected by ninhydrin [7 f 0.38 (d)/0.56 (l)] [43] Af-trifluoroacetyl-L-prolyl chloride for D,L-amphetamine separated with chloroform/methanol (197 3) and detected by sulfuric acid/formaldehyde (10 1) (Rf 0.49 (d)/0.55 (l)) [44] Af-benzyloxycarbonyl-L-prolyl chloride for D,L-methamphetamine separated with n-hexane/ethyl acetate/acetonitrile/diisopropyl ether (2 2 2 1) and detected by sulfuric acid/formaldehyde (10 1) [/ f 0.57 (l)/0.61 (d)] [44] (l/ ,2/ )-(-)-l-(4-nitrophenyl)-2-amino-1,3-propanediol (levobase) and its enantiomer dextrobase for chiral carboxylic acids separated with chloroform/ethanol/acetic acid (9 1 0.5) and detected under UV (254 nm) light R[ values 0.63 and 0.53 for 5- and / -naproxen, respectively) [45] (5)-(4-)-a-methoxyphenylacetic acid for R,S-ethyl-4-(dimethylamino)-3-hydroxybutanoate (carnitine precursor) with diethyl ether mobile phase [/ f 0.55 R)/0J9 (5)] [46] and (5)-(4-)-benoxaprofen chloride with toluene/acetone (100 10, ammonia atmosphere) mobile phase and fluorescence visualization (Zeiss KM 3 densitometer 313 nm excitation, 365 nm emission) (respective R values of R- and 5-isomers of metoprolol, oxprenolol, and propranolol were 0.24/0.28, 0.32/0.38, and 0.32/0.39) [47]. 

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