High-yielding multigram-scale

Via these optimized routes, the N-protected pyrimidine nucleoamino acids 6 and 9 were synthesized very efficiently in three high-yielding steps, starting from an inexpensive and commercially available serine derivative. The common intermediate O-MTM ether 3 can be synthesized on a multigram scale and is stable for years if stored in a refrigerator. 

Nitro substituents and heterocyclic nitrogen influence not only the yield of fluorodediazoniation but also the rate of decomposition which, in these cases, is too high to perform the reaction on a multigram scale. Some explosions have been reported. Thus, the decomposition of nitro-substituted or heterocyclic diazonium tetrafluoroborates is usually controlled by three-to fivefold dilution of these substrates in inert solids, such as acid-washed sand,113 218 Kiesel-guhr,3 sodium carbonate,3 barium sulfate,217 sodium fluoride,216 or sodium tetrafluoroborate.3 This modified technique has been generalized to the decomposition of all kinds of diazonium tetrafluoroborates under safe conditions, even on rather large scales. 

The most common and useful additives are copper(I) salts (such as CuCl), which produce high yields of 1 1 adducts in many cases.174 Several examples from the extensive work of the Ciba-Geigy group in Basel are compiled in Scheme 54, with an emphasis on subsequent conversions of the highly functionalized products into important heterocycles.175 These procedures are very simple and have been conducted on a multigram scale. Typically, the halogen component and the acceptor are heated without solvent at 110 °C in the presence of 1-10% CuCl. After several hours, the copper salts are removed by filtration and the product is isolated by distillation. It is clear that the copper additive behaves as more than just an initiator, the additions of electrophilic radicals to electron deficient alkenes like those shown in Scheme 54 would not be likely to succeed otherwise. 

As an example, thiolacetic acid was photoadded in high yield to butenyl aromatics in the multigram scale synthesis of compounds 35 (Scheme 3.23) [56], These products were, in turn, starting materials for the preparation of aryl-alkyl disulfides that were employed as protective agents for gold nanoparticles due to a passivation process. 

Photoinduced free-radical halogenation is very useful for the functionalization of electron-deficient alkenes such as vinyl halides. Among halides, the addition of bromine is by far the most useful reaction, as shown in Scheme 3.25. In the first example, a polyfluoroalkene was brominated in a high yield by using a 300 W light bulb as the light source. Of note, the synthesis of l,2,4-tribromo-l,l,2-trifluorobutane (38) was carried out under solvent-free conditions in a near-quantitative yield and on a multigram scale (Scheme 3.25a) [67]. l,2-Dibromo-l,l,2-trichloroethane (39) was likewise obtained in about 250 g amounts by the solar lamp irradiation of neat trichloroethylene to which bromine was continuously added (Scheme 3.25b) [68],... 

Lithiothiazoles are the starting material for the preparation of other metallated thiazoles. Thus, transmetallation of 2-lithiothiazole with trimethylsilyl chloride can be carried out in one-pot and multigram scale to give the stable and synthetically important 2-trimethylsilylthiazole 774. In the same way, 2- and 4-trimethylstannylthiazoles 775 and 776 can be obtained from the corresponding lithio derivatives and trimethyltin chloride. 4-Methyl-2-trimethylstannylox-azole reacts with a variety of aryl and heteroaryl halides and tetrakis(triphenylphosphine)palladium to give the 2-substituted products in high yield. 

Treatment of cycloserine with Fmoc-Cl or Fmoc-OSu in the presence of pyridine afforded a mixture of endo- and exocyclic N-acylated products (Fmoc = 9-fluorenylmethyloxycarbonyl). Selective protection of the primary amine was achieved on multigram scale and in high yield by in situ formation of the bis-silylated derivative with T,0-bis(trimethylsilyl)acetamide (BSA) followed by acylation (Scheme 76) <1998T15879>. 

In most cases, cyclopropene and its derivatives are easily prepared l5>. Especially the 3,3-disubstituted cyclopropenes can be obtained on a multigram scale in a two-step process 24-26) with overall yields as high as 80% (Eq. 1)... 

The alkyl 2-iodoalkanoates [5] can be formed in situ from the corresponding bromo compounds, which are more readily available, by the addition of a stoichiometric amount of sodium iodide to the reaction mixture. The products are obtained in high yields, which are similar to those obtained by direct use of flic iodo compound (Table 1, entries 2-6). The products can be synthesized without problems on a multigram scale. All of the alkyl 2-haloalkanoates [5] used in this reaction gave flic expected radical addition reaction. 

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