One-pot Two-step Process Research Articles

Oxidation of alkenes with hydrogen peroxide, catalyzed by boron trifluoride. Synthesis of vicinal methoxyalkanols

In oxidation of alkenes with the BF3-H2O2 system, boron trifluoride induces transfer of available oxygen from hydrogen peroxide, accompanied by the formation of epoxides. The oxidation in methanol occurs as a one-pot two-step process involving epoxidation of the C=C bond followed by opening of the oxirane ring, with the formation of methoxyalkanols.

Radiosynthesis of carbon‐11‐labelled GI181771, a new selective CCK‐A agonist

AbstractThe novel CCK‐A agonist, (S)‐3‐(3‐{1‐[(isopropylphenylcarbamoyl)methyl]‐2,4‐dioxo‐5‐phenyl‐2,3,4,5‐tetrahydro‐1H‐benzo[b][1,4]diazepin‐3‐yl}ureido)benzoic acid, GI181771 ((S)‐1) has been isotopically labelled with carbon‐11 at its urea site using [11C]phosgene in a one‐pot two‐step process, via the intermediate preparation of an [11C]isocyanate derivative. Optimized conditions for the preparation of (S)‐[11C]‐1 were the following: (1) Trapping of [11C]phosgene (radiosynthesized from cyclotron‐produced [11C]methane via [11C]carbon tetrachloride using minor modifications of published processes) at room temperature for 1–2 min in 300 µl of acetonitrile containing 0.6 µmol of the appropriate (structurally complex) chiral‐amine giving the corresponding [11C]isocyanate followed by (2) addition of an excess of 3‐aminobenzoic acid (40 µmol in 100 µl of THF) as the second amine giving the desired urea derivative (S)‐[11C]‐1 and (3) high‐performance liquid chromatography (HPLC) purification on a semi‐preparative Waters Symmetry® C18. Starting from a typical 1.2 Ci (44.4 GBq) batch of [11C]methane, 25–35 mCi (0.92–1.29 GBq, 6.8–9.6% decay‐corrected yield based on starting [11C] methane, n = 5) of (S)‐[11C]‐1 could be obtained within 35 min of radiosynthesis (HPLC purification and formulation as an i.v. injectable solution using a home‐made Sep‐pak®Plus C18 device included) with specific radioactivities ranging from 500 to 1500 mCi/µmol (18.5–55.5 GBq/µmol). The radiotracer preparation was a clear and colourless solution and its pH was between 5 and 7. As demonstrated by HPLC analysis, the radiolabelled product was found to be >99% chemically and radiochemically pure and the preparation was shown to be free of non‐radioactive precursors (starting amines) and radiochemically stable for at least 60 min. Finally, enantiomeric purity was found to be >99% according to chiral HPLC, demonstrating the absence of racemization during the process. Copyright © 2005 John Wiley & Sons, Ltd.

“One‐Pot” Two‐Step Synthesis of Aryl Sulfur Compounds by Photoinduced Reactions of Thiourea Anion with Aryl Halides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

One‐Pot Two‐Step Microwave‐Assisted Reaction in Constructing 4,5‐Disubstituted Pyrazolopyrimidines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 3-aminopyrazinone mediated by 2-pyridylthioimidate-ZnCl2 complexes. Development of an efficient route to a thrombin inhibitor.

A six-step preparation of thrombin inhibitor drug candidate 1 from pyrazinone 7 in 47% overall yield is described. The problem of low reactivity between weak amine nucleophile 4 and poor electrophile 3-bromopyrazinone 17 was overcome with the use of pyridinylthioimidate 27 in the presence of ZnCl(2) to afford adduct 3 in high yield. Several zinc complexes were characterized by solution and solid-state NMR and X-ray crystallographic analyses, and provided insight into the reaction mechanism. Preparation of pyridine N-oxide amine 4 was accomplished via a selective oxidation of the corresponding pyridinylamine 6. Pyridinylthioimidate 27 was prepared from pyrazinone 7 via a two-step one-pot process in near quantitative yield. Chlorination of the pyrazinone ring in 3 followed by hydrolysis and amide coupling completed the synthesis of 1. This chromatography-free synthesis was used successfully to prepare multikilogram quantities of the drug with reproducibility and high purity.

One-pot two-step microwave-assisted reaction in constructing 4,5-disubstituted pyrazolopyrimidines.

[reaction: see text] A microwave-assisted reaction was developed to facilitate the construction of 4,5-disubstituted pyrazolopyrimidines. This one-pot two-step process involves a sequential S(N)Ar displacement of the C4 chloro substituent with various anilines and amines, followed by a Suzuki coupling reaction with different boronic acids. Using microwave irradiation leads to high product conversion, low side product formation, and shorter reactions.

Trimethylsilyl triflate promoted addition of allyltributylstannane to aldonitrones; one-pot synthesis of 5-iodomethylisoxazolidines

the trimethylsilyl triflate promoted allylation of nitrones with allyltributylstannane affords O-silylated hydroxylamines in high yield; when the crude reaction mixture is quenched with N-iodosuccinimide, 5-iodomethylisoxazolidines are formed in excellent yields. The overall one-pot two-step process represents a valuable improvement in terms of time, cost and overall yield with respect to the previously reported three stage procedure involving nitrone allylation, hydroxylamine O-silylation, and iodocyclisation.

Concise allene synthesis from propargylic alcohols by hydrostannation and deoxystannylation: A new route to chiral allenes

Propargylic alcohols were converted to allenes in a two-step one-pot process comprised of hydrostannation of propargylic alcohols and subsequent deoxystannylation. Chiral ( S)-2,3-decadiene of high enantiomeric excess (ee) can be prepared in a similar way.