4541-32-6Relevant academic research and scientific papers
Stereochemical Effects in the Gas-Phase Pinacol Rearrangement of cis- and trans-1,2-Dimethylcyclopentane-1,2-diol
Petris, Giulia de,Giacomello, Pierluigi,Picotti, Tito,Pizzabiocca, Adriano,Renzi, Gabriele,Speranza, Maurizio
, p. 7491 - 7495 (1986)
The pinacol rearrangement of cis- and trans-1,2-dimethylcyclopentane-1,2-diol, promoted by the gaseous Broensted acids D3+, CH5+/C2H5+, and t-C4H9+, was studied by mass spectrometric and radiolytic methods.Dehydration of the protonated substrate is rate limiting, and competitive experiments with pinacol, carried out at high pressure (760 torr), showed that the cis rearranges more rapidly than the trans isomer, indicating participation of the migrating methyl group to the leaving water molecule.The results are compared with those concerning the same substrates in solution, where no evidence of anchimeric assistance was found.
Preparation method of 2, 2-dimethyl cyclopentanone
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Paragraph 0022, (2021/06/23)
The invention discloses a preparation method of 2, 2-dimethyl cyclopentanone, which comprises the following steps: methylating 2-methoxycarbonyl cyclopentanone to obtain a methylated product 2-methyl-2-methoxycarbonyl cyclopentanone, carrying out keto-carbonyl protection on the methylated product to obtain a protected product 2-methyl-2-methoxycarbonyl cyclopentanone ketal, carrying out ester group reduction on the protection product to obtain an alcohol product 2-hydroxymethyl-2-methyl cyclopentanone ketal, carrying out deprotection on the alcohol product under an acidic condition to obtain a deprotection product 2-hydroxymethyl-2-methyl cyclopentanone, and brominating the deprotection product to obtain 2-bromomethyl-2-methyl cyclopentanone. All raw materials adopted by the method are low in cost and easy to obtain in the market, and reactions in all steps are conventional reactions and easy to implement; the process is simple, mild in reaction condition and easy to operate; the reaction time is short, control is easy, the yield of each step is 90% or above, and industrial large-scale production is easy to achieve.
METHOD FOR INTRODUCING SUBSTITUENT INTO alpha,beta-UNSATURATED KETONE AND METHOD FOR SYNTHESIZING PROSTAGLANDIN USING THE SAME
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Paragraph 0044-0046, (2021/11/20)
The present invention provides a method for introducing substituents into the α-position and the β-position of an α,β-unsaturated ketone, which not only can be used for the synthesis of a prostaglandin by a three-component coupling process, but also enables synthesis of a prostaglandin in a high yield by one-pot operation without requiring the use of a large excess amount of any of the three components required for the synthesis or using a highly toxic heavy metal as a catalyst or a solvent that is highly toxic to living bodies, and a method for synthesizing a prostaglandin using the same technical means. The method for introducing substituents into an α,β-unsaturated ketone according to the present invention is a method for introducing substituents into the carbon at the α-position and the carbon at the β-position of an α,β-unsaturated ketone, including: a first step of mixing alkyllithium and trialkylalkenyl tin in which tin atom binds to the vinyl position of the alkenyl group; a second step of mixing the mixture of the first step and dialkylzinc; a third step of mixing the mixture of the second step and an α,β-unsaturated ketone; and a fourth step of mixing the mixture of the third step and a trifluoromethanesulfonate compound.
Organozinc-aided, HMPA-free, stoichiometric three-component coupling for the general synthesis of prostaglandins and stable prostacyclin analogs with biological significance
Koyama, Hiroko,Izumiseki, Atsuto,Suzuki, Masaaki
, p. 1467 - 1470 (2019/05/07)
A three-component coupling procedure was developed to construct the entire prostaglandin (PG) skeleton under HMPA-free and stoichiometric conditions via a combination of dimethylzinc-aided conjugate addition of an ω-side-chain vinyllithium with (R)-4-hydroxy-2-cyclopentenone and the direct trapping of the resulting enolate with an α-side-chain propargyl triflate. Dimethylzinc effectively regulated both the conjugate addition and alkynylation reactions. Thus, the method afforded protected 5,6-didehydro-PGE2, a common intermediate for the general synthesis of natural PGs and the stable artificial prostacyclin (PGI2) analog isocarbacyclin in 88% yield. The utility of the method was further applied to the syntheses of novel intermediates, which are useful for the straightforward synthesis of 15R-TIC and 15-deoxy-TIC in 79% and 86% yield, respectively.
Regioselective Dialkylations of N-(tert-Butyl)iminocyclopentane via Deprotonating One-Pot Procedures
Knorr, Rudolf,Neuner, Brigitte
, (2018/06/04)
The title compound (1) was chosen as a model for the α/α′-regioselectivity of deprotonation and subsequent alkylation adjacent to the C=N bond. With the bulky base lithium N,N-diisopropylamide (LDA) as a catalyst, the one-pot deprotonation steps can be performed through titration with methyllithium, using gas-volumetric observation of the liberated methane. In the first step with ensuing methylation by iodomethane, the primary product is born at ?40?°C in its metastable (Z) configuration (kinetic control) and may be either isolated or converted in?situ at 30?°C into its thermodynamically favored (E)-isomer via cis to trans stereoinversion at the N-atom. Being slow enough on the laboratory time scale, this stereoinversion process can serve to control the regioselectivity of the second deprotonation/alkylation sequence as follows. The α,α′-products are formed from the intermediate (Z)-imine, whereas α,α-products result from the intermediate (E)-imine; in either case, syn deprotonation (cis to tBu at nitrogen) by LDA is apparently disfavored by the tBu group, so that anti deprotonation becomes obligatory. If a third one-pot deprotonation step is too slow with LDA, it may be performed with the stronger base butyllithium/HMPA which, however, reacts regio-unselectively. Regioselective one-pot, LDA-catalyzed deprotonation with alkylation by oxiranes (alone, or alternatingly with iodomethane) opens a short access to spiro-[2.4]heptan-4-ones.
SUBSTITUTED HETEROCYCLIC AMINE COMPOUNDS AS CHOLESTRYL ESTER-TRANSFER PROTEIN (CETP) INHIBITORS
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Page/Page column 24; 25, (2013/03/26)
The present application relates to cycloalkylpyridin-2-amines derivates of formula (I) or stereoisomers thereof or pharmaceutically acceptable salts thereof. The present application also relates to the process for the preparation of compounds of formula (I). The present application further describes the compounds of formulat (I) as cholesteryl ester-transfer protein (CETP) inhibitors. The present application further relates to pharmaceutical compositions comprising compounds of formula (I) or stereoisomers thereof or pharmaceutically acceptable salts thereof.
Catalytic asymmetric synthesis of a tertiary benzylic carbon center via phenol-directed alkene hydrogenation
Caille, Seb,Crockett, Rich,Ranganathan, Krishnakumar,Wang, Xiang,Woo, Jacqueline C. S.,Walker, Shawn D.
, p. 5198 - 5206 (2011/08/09)
An expeditious synthetic approach to chiral phenol 1, a key building block in the preparation of a series of drug candidates, is reported. The strategy includes a cost-effective and readily scalable route to cyclopentanone 3 from isobutyronitrile (10). The sterically hindered and enolizable ketone 3 was subsequently employed in a challenging Grignard addition mediated by LaCl 3?2LiCl. A novel preparation of the lanthanide reagent required for this transformation is described. To complete the process, a highly enantioselective hydrogenation step afforded the target (1). The importance of the phenol group to the success of this asymmetric transformation is discussed.
Cyclic amino acids and derivatives thereof useful as pharmaceutical agents
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, (2008/06/13)
The invention is a novel series of cyclic amino acids which are useful in the treatment of epilepsy, faintness attacks, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, gastrointestinal disorders such as irritable bowel syndrome (IBS), and inflammation, especially arthritis. A pharmaceutical composition containing a compound of the invention as well as methods of preparing the compounds and novel intermediates useful in the preparation of the final compounds are included.
Cyclic ketones, their preparation and their use in the synthesis of amino acids
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, (2008/06/13)
A method is provided for making an enantiomerically pure of the formula: in which R and R′ represent C1?C10 alkyl, C2?C10 alkenyl or C3?C10 cycloalkyl and the wedges signify (S)- or (R)-stereochemistry, the substituents in compound (II) being trans. Conjugate addition is carried out between an organometallic nucleophile that provides a group R as defined above and (R)-4-acetoxycyclopent-2-en-1-one, (S)-4-acetoxycyclopent-2-en-1-one or a similar compound in which acetoxy is replaced by another leaving group to give, e.g. in the case of the acetoxy compound, a trans 3,4-disubstituted addition product of formula III or IV; The acetyl group is eliminated from the addition product to give an (R)- or (S)-4-alkyl or 4-alkenyl cyclopent-2-en-1-one the compound of formula is then to be hydrogenated to give a cyclopentanone of formula (I) or conjugate addition of a second organometallic nucleophile that provides a group R′ as defined above to the compound of the above formula may be carried out to give a trans 3,4-disubstituted addition product of formula (II). One of the above compounds may be converted e.g. via an intermediate (XV)-(XVIII) (in which the substituents R and R′ and the wedges have the meanings indicated above) to a gabapentin analogue of one of the formulae shown below: in which the substituents R and R′ and the wedges also have the meanings indicated above.
Amidino derivatives useful as nitric oxide synthase inhibitors
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, (2008/06/13)
The current invention discloses useful pharmaceutical compositions containing amidino derivative useful as nitric oxide synthase inhibitors.
