Amines oxycarbonylation

Reaction of 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l, 2,3- e]-1,4-ben-zothiazine-6-carboxylic acid and its ethyl ester with B(OH)3 in AC2O in the presence of ZnCl2 afforded 6-[(diacetoxyboryl)oxycarbonyl] derivative 323 (R = OAc)], which was reacted with primary and cyclic amines to give 10-amino-9-fluoro-7-carboxylic acid derivatives 324 (97MI41, 98MI30). 6-[(Difluoroboryl)oxycarbonyl derivative 323 (R = F) was obtained from ethyl 9,10-difluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazine-6-carboxylate with BF3-THF complex. Reaction of 323 (R = F) and 1-methylpiperazine in DMF at 50-60 °C and subsequent acidic hydrolysis afforded 7 (97MI1). 

Eine ahnliche Umwandlung von sekundaren Alkoholen in primare Amine mittels der Mit-sunobu-Reaktion ist am Beispiel dcr 7-Hydroxy- untersucht worden1. Behandlung dieser Alkohole mit Triphenylphosphan, Phthalimid und Dieth-oxycarbonyl-diazen in Tetrahydrofuran ergibtdie 2-Phthalimido-Derivate, die isoliert und mittels Hydrazin unter Bildung der freien Amine gespalten werden. Bei dem beschriebenen System entstehen auf diese Weise aus den 7-m/o-Alkoholen die 7-exo-Amine und aus den 7-exo-Alkoholen Gemische der 1-endo- und 7-eJto-Amine. 

It has been reported that tertiary amines (as additives or as the solvent) lead to increased yields when etherifying tyrosine derivatives with polystyrene-bound benzyl alcohols [175]. Nevertheless, other phenols react smoothly without the addition of a base [47,176], When only a slight excess of phenol is used for the etherification of support-bound alcohols, AyV -bi s (eth oxycarbonyl)hydrazi n e (the by-product of the Mit-sunobu reaction) can compete with the phenol to a significant extent and become attached to the support. This reaction can be suppressed by the use of a greater excess of phenol [168]. 

Protection of amines.1 The reagent can be used to prepare N-fluorenylmeth-oxycarbonyl (Fmoc) amino acids (70-99% yield). 

The oxycarbonylation of phenol in the presence of a palladium catalyst, a tertiary amine and a manganese cocatalyst at room temperature and atmospheric pressure results in the formation of diphenyl carbonate in good yield (equation 184).453... 

A related oxycarbonylation of secondary amines to A/ JV-disubstituted ureas in the presence of copper(I) salts at room temperature and atmospheric pressure has been disclosed by Brackman.6263 The reaction is particularly effective with cyclic secondary amines such as piperidine and morpholine (equation 293), with primary and aliphatic secondary amines being much less reactive.6263... 

Polymer-immobilised catalysts containing gold particles smaller than 10 nm have been prepared by impregnating Merck Ion Exchanger IV with HAuCU, and have been used to synthesise ureas and carbamates by reaction of amines with carbon monoxide and oxygen 16 so for example the oxycarbonylation of aniline proceeded at 448 K and 5 MPa pressure (C0 02 = 2 l) in 1-3 h to give yields of up to 99% of phenylmethyl-carbamate (Scheme 13.3). 

Many reactions that produce specific numbers and/or distributions of TV-substituents, or combinations of different TV-substituents, have been devised. The protecting groups boc (t-butyl-oxycarbonyl)104 and trityl (triphenylmethyl)105 are convenient since they can be removed under mild conditions. C-Substitution can alter the relative reactivity of nitrogen atoms by steric or inductive effects to determine substitution patterns (e.g., for the bis(l,2-cyclohexdiyl) cyclam (23), which preferentially bis-substitutes at the six and 16 sites).101 The presence of imine or amide functions also determine substitution patterns and the substituted imine or amide macrocycles can be reduced to the substituted cyclic amine. 

The iprovalicarb molecule contains two chiral centers the configuration of the stereocenter in the amino acid function is defined by the use of L-valine as a natural amino acid component. The amine portion of the molecule is racemic, so the active substance contains two diastereomers (the S,S- and S,R-diastereomers). Iprovalicarb (3) is made up of three building blocks the carbamate component isopropyloxycarbonyl, the natural amino acid L-valine (11), and the amine unit p-methylphenylethylamine (15). In the first step, isopropyl chloroformate (10) is treated with L-valine (11) in aqueous sodium hydroxide solution to give isopropyl-oxycarbonyl-L-valine (12) (Scheme 18.2). 

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