ABSTRACT
Pd-catalyzed aminocarbonylation between aryl bromide and NH-benzazepinone was effectively carried out to furnish the key intermediate for tolvaptan (up to 85%) in one step.
Subject(s)
Benzazepines/chemical synthesis , Chemistry, Pharmaceutical/methods , Catalysis , Palladium/chemistry , Tolvaptan , Vasopressins/chemical synthesisABSTRACT
Catalytic disulfenylation reaction of alkenes by common Lewis acids has been investigated in detail. While reactions by FeCl(3) were feasible with cycloalkenes and other simple alkenes, much faster and excellent conversions were possible by AlCl(3) even with the substrates less reactive toward FeCl(3).
Subject(s)
Alkenes/chemistry , Disulfides/chemistry , Catalysis , Chlorides , Cycloparaffins/chemistry , Ferric Compounds/chemistry , Molecular StructureABSTRACT
Continuing search for beneficial additive toward the Beckmann rearrangement (BR) of indanone oxime has revealed that common Lewis acid catalyst in methanesulfonyl chloride (MsCl) showed increasing efficiency in this ionic rearrangement. The new protocol with MsCl is superior to the classical phosphorus-based methods such as PPA and Eaton reagent, especially in the reaction of indanone oximes.
Subject(s)
Indans/chemical synthesis , Oximes/chemistry , Amides/chemistry , Catalysis , Mesylates , Oximes/chemical synthesis , SolventsABSTRACT
New and effective method for the Beckmann rearrangement of indanone oxime mesylate is described, in which a selective and controlled production of the isomeric isocarbostyrils is achieved.
Subject(s)
Isoquinolines/chemical synthesis , Mesylates/chemistry , Oximes/chemistry , Indicators and Reagents , Isomerism , Solvents , Titanium/chemistryABSTRACT
A combined system of bismuth triflate [Bi(OTf)(3)] and boron trifluoride etherate (BF(3).OEt(2)) in dichloromethane is an efficient promoter for the glycosylation of N-acetylneuraminic acid derivatives. The co-existence of two acid catalysts such as Bi(OTf)(3)-BF(3).OEt(2) or Bi(OTf)(3)-PPA is confirmed to be essential for obtaining high yields of glycosylation products with p-nitrobenzyl alcohol, which also turned to be superior to those reported previously.
Subject(s)
Acetates/chemistry , Boranes/chemistry , Mesylates/chemistry , Sialic Acids/chemistry , Benzyl Alcohol/chemistry , Catalysis , Glycosides/chemistry , Glycosylation , Models, Chemical , Nitro Compounds/chemistry , Solvents , TemperatureABSTRACT
We have surveyed the utility of Beckmann rearrangement for the conversion of indanones into carbostyrils. Initial attempts at the conversion of 6-methoxy indanone oxime under classical conditions resulted in the formation of the two unusual products: 2-sulfonyloxyindanone and the dimeric product. This unusual rearrangement was also observed by the treatment of some metal triflates species. Further investigation has led to the development of reliable conditions starting from oxime mesylate (not oxime tosylate), in which some strong Lewis acid catalyst (ZrCl(4)) was employed in either a conventional or non-conventional solvent system. The advantage of the new protocol is highlighted by the simple work up and direct isolation of the product in 65% isolated yield.
Subject(s)
Hydroxyquinolines/chemical synthesis , Indans/chemistry , Oximes/chemistry , Quinolones , Alkanesulfonates/chemistry , Catalysis , Chlorides , Hydroxyquinolines/pharmacology , Indans/pharmacology , Isomerism , Mesylates/chemistry , Metals/chemistry , Organometallic Compounds/chemistry , Solvents , ZirconiumABSTRACT
The dimeric derivative of aripiprazole was synthesized via the two notable synthetic technologies as a key step: (1) efficient aldehyde bis-arylation by Bi(OTf)(3) and (2) facile Wynberg amination at room temperature. The synthesis has established the structural identity with the minor contaminant sometimes present in Aripiprazole.
Subject(s)
Antipsychotic Agents/chemical synthesis , Piperazines/chemical synthesis , Quinolones/chemical synthesis , Amination , Antipsychotic Agents/chemistry , Aripiprazole , Dimerization , Drug Contamination , Piperazines/chemistry , Quinolones/chemistryABSTRACT
Careful base and solvent optimization for catalytic amination is described. A Pd-catalyzed amination between some arylbromide and unprotected piperazine (1equiv) was efficiently carried out with Pd/BINAP catalyst in a toluene-DBU solvent system, which is useful for the one-pot preparation of unsymmetrical piperazine through amination and in-situ N-protection. Reaction with N-BOC-piperazine was also successful in toluene-DBU or more polar NMP with Cs(2)CO(3) as a key base. No reports have previously reported such solvent and base optimization in arylpiperazine synthesis.
Subject(s)
Piperazines/chemical synthesis , Amination , Benzene Derivatives/chemical synthesis , Catalysis , Indicators and Reagents , Naphthalenes/chemistry , Palladium/chemistry , Solvents/chemistryABSTRACT
In our solvent optimization study of NaBH(4) reduction, NMP was found to enhance the reactivity. A chemoselective debromination of the bromide and sulfonates can be attained in the new borohydride reagent system: NaBH(4)-LiOTf-NMP. This mixed system worked as an alternative to NaBH(3)CN and Bu(3)SnH for the S(N)2 type displacement of alkylbromide and sulfonate. Also mentioned is an expedient reduction of an azide group into amine by NaBH(4) in NMP without any additive, which offers a convenient protocol for the direct transformation of halides into amines via azide in one flask. Some examples of other reductions were also presented.
Subject(s)
Borohydrides/chemistry , Pyrrolidines/chemistry , Azides/chemistry , Chemistry, Pharmaceutical/methods , Hydrocarbons, Brominated/chemistry , Oxidation-Reduction , Solvents/chemistryABSTRACT
Attempted Beckmann rearrangement of the 6-methoxyindanone oximes in conventional conditions resulted in the formation of the two kinds of unexpected products: 2-sulfonyloxyindanone and the dimeric product. Related rearrangement was also observed in the reaction with RhCl-trifluoromethansulfonic acid system.
Subject(s)
Indans/chemistry , Oximes/chemistry , Quinolones , Catalysis , Hydroxyquinolines/chemistry , Indicators and Reagents , Isomerism , Magnetic Resonance SpectroscopyABSTRACT
An efficient synthesis of alpha,beta-unsaturated ketones by the reaction of acid chlorides with trialkylaluminum (1/3 mole equiv) in the presence of AlCl(3) (1 mol equiv) is described. Dialkylzincs were also useful and are easier to prepare than trialkylaluminum. Reaction of RCOCl with R'AlCl(2) or R'(2)AlCl gave R'COR, without AlCl(3), in high yield.
