17465-36-0Relevant academic research and scientific papers
Synthesis of ketamine from a nontoxic procedure: a new and efficient route
Fareghi-Alamdari, Reza,Momeni-Fard, Behnaz,Zekri, Negar
, (2020/10/02)
Abstract: Ketamine [2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one]has been used in both veterinary and human medicine. In this research, a new and efficient protocol has been developed for the synthesis of ketamine, by using hydroxy ketone intermediate.Synthesis of this drug has been done in five steps. At first, the cyclohexanone was made to react with 2-chlorophenyl magnesium bromide reagent followed by dehydration in the presence of an acidic ionic liquid, 1-methyl-3-[2-(dimethyl-4-sulfobutyl-ammonium) ethane] imidazolium hydrogen sulfate to obtain 1-(2-chlorophenyl)-cyclohexene. The oxidation of the synthesized alkene by potassium permanganate gave corresponding hydroxy ketone intermediate. The imination of this intermediate by methyl amine and finally the rearrangement of the obtained imine at elevated temperature resulted in the synthesis of ketamine. All of the intermediates and the product were characterized by 1H-NMR and IR spectroscopies. No need to use toxic bromine (which is used in most of the reported procedures for the synthesis of ketamine), high reaction yields and use of commercially available and safe materials and no need to use corrosive acids in the dehydration step are some of the advantages of this procedure over the common reported ones for the snthesis of ketamine. Graphic abstract: An efficient five-step protocol for the synthesis of ketamine was developed. Cyclohexanone reacted with 2-chlorophenyl magnesium bromide, followed by dehydration with acidic ionic liquid. Oxidation of the alkene gave corresponding hydroxy ketone intermediate.The imination of this intermediate and rearrangement of the obtained imine finally produced ketamine.[Figure not available: see fulltext.]
Novel enantioselective synthesis of (S)-ketamine using chiral auxiliary and precursor Mannich base
Gohari, Seyed Jamaladdin,Javidan, Abdollah,Moghimi, Abolghasem,Taghizadeh, Mohammad Javad,Iman, Maryam
, p. 331 - 336 (2019/05/07)
Ketamine has been extensively used as an anesthetic drug. Chiral auxiliaries such as tert-butanesulfinamide (TBSA) can be used for the asymmetric synthesis of (S)-ketamine. Condensation of TBSA with ketones provides tert-butanesulfinylimines in consistently high yields. The tert-butanesulfinyl group actuates the imine for nucleophilic addition, is a potent chiral directing group, and after nucleophilic addition is easily dissociated by intervention with acid solution. To prepare 2-(N-piperidinomethyl)-1-phenylcyclohexylamine (1), we started with the cyclohexanone and using Mannich reaction achieved an aminoketone. Then, we made the sulfiniylamin (2) by the condensation of TBSA with aminoketone. By using salts such as Ti(OEt)4, we obtained N-tert-butanesulfinylketimine in 85% yield. Next, we provided a new chiral center (3) using Grignard reagent as nucleophile at -78 °C (80% yield). Finally, after many steps, the (S)-ketamine synthesized under ozonolysis conditions, with good yield and enantioselectivity (75% yield and 75% ee).
SOLID ORAL DOSAGE FORMS OF 2R,6R-HYDROXYNORKETAMINE OR DERIVATIVES THEREOF
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Page/Page column 38, (2018/01/17)
This invention relates to solid oral dosage forms of 2R,6R-hydroxynorketamine or prodrugs thereof having Formula Ib, including any pharmaceutically acceptable salt of the foregoing, for use in a therapeutic method for the treatment of a depressive disorder in a patient.
Functionalization of unactivated alkenes through iridium-catalyzed borylation of carbon-hydrogen bonds. Mechanism and synthetic applications
Olsson, Vilhelm J.,Szabo, Kalman J.
supporting information; experimental part, p. 7715 - 7723 (2010/02/28)
(Chemical Equation Presented) This paper describes an efficient carbon-carbon bond formation reaction, which is based on carbon-hydrogen bond functionalization of unactivated alkenes. This process is based on in situ generation of allylic and vinylic boronates by iridium-catalyzed borylation of alkenes followed by carbon-carbon bond formation reactions. The selectivity of the carbon-hydrogen bond functionalization can be efficiently controlled for cyclic alkenes. By using additives, such as methylimidazole and DBU, the iridium-catalyzed borylation led to formation of allyl boronates, which reacted with aldehydes in a one-pot sequence affording stereodefined homoallylic alcohols. Cycloalkenes without additives aswell as acyclic substrates gave vinylic boronates, which were coupled with organohalides in a Suzuki-Miyaura sequence. By this process allylic and vinylic silabutadiene derivatives can be prepared from allylsilanes with excellent regio- and stereoselectivity. The mechanism of the carbon-hydrogen bond functionalization based on the borylation reaction was explored by isotope labeling experiments, measuring the kinetic isotope effect and study of the effects of the additives on the selectivity of the process. It was concluded that the reactions proceed via a dehydrogenative borylationmechanism,which shows analogous features with the palladium-catalyzed Heck coupling reaction.
Selective one-pot carbon-carbon bond formation by catalytic boronation of unactivated cycloalkenes and subsequent coupling
Olsson, Vilhelm J.,Szabo, Kalman J.
, p. 6891 - 6893 (2008/09/17)
(Chemical Equation Presented) Two channels: Cycloalkenes can be selectively functionalized by iridium-catalyzed boronation followed by Suzuki coupling with an aryl iodide or reaction with an aldehyde. The selectivity for allylic and vinylic functionalization can be controlled by a slight change of the reaction conditions. DBU = 1,8-diazabicyclo-[5.4.0]undec-7-ene, pin = pinacol.
