Rapid synthesis

Of interest is a recent report of a rapid synthesis of efaroxin (51), a potent, selective O2 adrenoceptor antagonist, using Darzens Reaction. Accordingly, a-bromoester 48 was condensed with aldehyde 47. The glycidic ester (49) was then hydrogenated to reduce the more labile epoxide bond to give alcohol 50. Subsequent standard transformations subsequently lead to a completed 4-step synthesis of efaroxin. o... 

Moody s synthesis of promothiocin 43 provided evidence that the Bohlmann-Rahtz method can be used for the rapid synthesis of complex pyridines. Oxazaole 44 was treated with alkynyl ketone 45 to afford 46 in 83% yield. The ester moiety of 46 was elaborated into a thiazole substituent providing entry into the northeast quadrant of 43. 

Probably the most widely applicable asymmetric imine aziridination reaction reported to date is that of Wulff et al. These workers approached the reaction from a different perspective, utilizing the so-called vaulted , axially chiral boron Lewis acids VANOL and VAPOL [35] to mediate reactions between ethyl diazoacetate and N-benzhydrylimines (Scheme 4.29) [36]. The reactions proceed with impressive enantiocontrol, but there is a requirement that the benzhydryl substituent be present since this group is not an aziridine activator there is, therefore, a need for deprotection and attachment of a suitable activating group. Nonetheless, this method is a powerful one, with great potential for synthesis, as shown by the rapid synthesis of chloroamphenicol by the methodology [37]. 

The rapid synthesis of heteroaromatic Hantzsch pyridines can be achieved by aromatization of the corresponding 1,4-DHP derivative under microwave-assisted conditions [51]. However, the domino synthesis of these derivatives has been reported in a domestic microwave oven [58,59] using bentonite clay and ammoniiun nitrate, the latter serving as both the source of ammonia and the oxidant, hi spite of some contradictory findings [51,58,59], this approach has been employed in the automated high-throughput parallel synthesis of pyridine libraries in a 96-well plate [59]. In each well, a mixture of an aldehyde, ethyl acetoacetate and a second 1,3-dicarbonyl compound was irradiated for 5 min in the presence of bentonite/ammonium nitrate. For some reactions, depending upon the specific 1,3-dicarbonyl compound used. 

The rapid synthesis of 4-thiazolidinones by the MCR of an amine, aldehyde and mercaptoacetic acid has been developed under microwave-assisted conditions [73-75]. Irradiation of the three components in ethanol at 120 °C in the presence of molecular sieves [73] or in toluene at reflux under atmospheric conditions [74] in a single-mode microwave synthesizer gave the... 

The rapid synthesis of 1,2,4-triazines has also been developed under microwave-assisted conditions [80]. Irradiation of a 1,2-diketone with acyl hydrazides and ammonium acetate for 5-10 min at 180 °C in a single-mode microwave reactor gave 3,5,6-trisubstituted 1,2,4-triazines in excellent yield and purity and reaction times that were reduced 60-300 fold over conventional conductive heating methodology (Scheme 22). 

Bazureau et al. have reported a similar protocol to that described in Sect. 8.1 for the rapid synthesis of 2-thioxo tetrahydropyrimidin-4-(lH)-ones via cycli-zation of a primary amine with an isothiocyanate and a /1-dielectrophile (Fig. 35) [138]. First a j6-amino ester was linked to the ionic hquid support... 

Combinatorial chemistry has become of increasing importance, particularly within drug companies, in allowing the very rapid synthesis of large numbers of candidate molecules which require characterization and testing for their effectiveness. An important part of the characterization of any molecule is the determination of its molecular weight and LC-MS has been used extensively for this purpose. With... 

Considerable interest has been focused on the efficient and rapid synthesis of 2-deoxy-2-[ F]fluoro-D-gIucose, a popular imaging agent for positron-emission tomography (see Section III, 1). However, introduction of a fluorine atom at C-2 by nucleophilic displacement is generally not easy on account of the weak nucleophilic character of the fluoride ion. One possible... 

Syntheses of 3-deoxy-3-fluoro sugars are described next. A rapid synthesis aimed at 3-deoxy-3-[ F]fluoro-D-glucose ( F-3DFG) was developed. ... 

Jmai", Y.i Rapid Synthesis of Polyimides from Nylon-Salt Monomers. Vol. 140, pp. 1-23. 

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

Peng Y, Song G (2001) Simultaneous microwave and ultrasound irradiation A rapid synthesis of hydrazides. Green Chem 3 302-304... 

Wu C, Mosher BP, Zeng T (2006) Rapid synthesis of gold and platinum nanoparticles using metal displacement reduction with sonomechanical assistance. Chem Mater 18 2925-2928... 

Another approach to the rapid synthesis of complex polycycles from simple acyclic compounds is via the Ni(COD)2-catalyzed reaction of an enone containing an alkyne moiety to give a carbo- or heterocyclic intermediate, which is quenched with an electrophile. A typical transformation as shown by Montgomery and his group... 

The reaction conditions should be optimized prior to scale-up. As the in vivo system is mainly used for initial metabolite characterization, the goal of reaction optimization is finding suitable conditions (not necessary the optimal conditions) to enable rapid synthesis of small amounts of the desired metabolite at a reasonable cost. 

An improved synthesis of nC-2 thymine 49, for use in PET scans, was made possible by an efficient and rapid synthesis of nC-phosgene, previously reported <02NMB345> by the same authors. nC is a particularly interesting challenge due to its very short half life (20 minutes) and the whole sequence and purification from the end of the bombardment took 16 minutes. The scale was necessarily small (0.2 mg) <06TL5321>. 

A rapid synthesis of carbon-14 labeled [l-14C]levulinic acid from simple building blocks has been demonstrated by Johansen and coworkers (Scheme 6.172) [324], In all three of the synthetic steps, starting from bromo[l-14C]acetic acid, microwave heating was used to accelerate the reactions, allowing a total preparation time of less than 1 h. The labeled levulinic acid was subsequently transformed into (5Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone in a bromination/oxidation sequence (not shown), a potent quorum sensing inhibitor. 

MW heated reactions in homogeneous media, using either neat reagents or in the presence of solvents, may also be performed at atmospheric pressure. This approach has been used particularly by Bose et al. [17]. (MORE Chemistry), who reported, for example, the rapid synthesis of heterocycles [18] in open vessels. Another approach, which avoids hazards due to the flammability of solvents, is to perform the reactions under reflux in a MW oven, which is modified to allow the reaction vessel to be attached to a reflux condenser outside the MW oven [7, 19]. It should be pointed out, however, that most of the available evidence shows that rate enhancements of MW heated reactions in homogeneous media at atmospheric pressure are small or nonexistent [19], This will be discussed in more detail later in this review (see also Chapt. 5 of this book). 

A simple and rapid synthesis of tetrapyrrolic macrocycle has been achieved under dry media conditions with microwave activation. Pyrrole and benzaldehyde adsorbed on silica gel afford tetraphenylporphyrin within 10 min (Scheme 8.26), whereas with conventional methods (e. g. acetic acid in the presence of pyridine) 24 h were necessary. 

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