3779-29-1

Usage

Uses

Used in Pharmaceutical Industry:
Diethyl 1,1-cyclobutanedicarboxylate is used as a pharmaceutical intermediate for the production of Carboplatin, a widely used chemotherapy drug for the treatment of various types of cancer, including testicular, ovarian, bladder, and lung cancers. It plays a vital role in the synthesis process, contributing to the development of life-saving medications.
Used in Chemical Synthesis Studies:
Diethyl cyclobutane-1,1-dicarboxylate may also be utilized in chemical synthesis studies, where it can serve as a key component in the development of new compounds and materials. Its unique structure and properties make it a valuable asset in the field of chemical research and development.

Preparation

The preparation of diethyl 1,1-cyclobutanedicarboxylate is as follows:The major product is tetraethy1 1,1,5,5-pentanetetra-carboxylate II with diethyl malonate. To eliminate this side reaction, II was independently prepared by the addition of hydrogen bromide to diethyl allylmalonate (I) and then cyclized to II by treatment with sodium ethylate. The over-all yield from I is about 50%.

InChI:InChI=1/C10H16O4/c1-3-13-8(11)10(6-5-7-10)9(12)14-4-2/h3-7H2,1-2H3

Upstream product

• 18719-43-2 diethyl (3-chloropropyl)malonate 
• 10149-21-0 diethyl 2-(3-bromopropane)malonate 
• 141-52-6 sodium ethanolate 
• 5445-51-2 cyclobutane-1,1'-dicarboxylic acid 
• 109-70-6 1.3-chlorobromopropane 
• 105-53-3 diethyl malonate 
• 996-82-7 sodium diethylmalonate 
• 109-64-8 1,3-dibromo-propane 
• 64-17-5 ethanol 
• 142-28-9 1,3-Dichloropropane 
• 5469-66-9 propane-1,3-diol ditosylate 
• 5162-44-7 1-bromo-4-butene 
• 28438-55-3 2-(3-Ethylsulfanyl-propyl)-malonic acid diethyl ester 

Downstream Products

• 4415-82-1 cyclobutanemethanol 
• 4399-47-7 Bromocyclobutane 
• 77500-71-1 4-(5,8-Dioxo-6,7-diaza-spiro[3.4]oct-6-yl)-2-hydroxy-benzoic acid ethyl ester 
• 277756-42-0 1-trifluoromethyl-cyclobutanecarbonyl fluoride 
• 277756-45-3 (1-trifluoromethyl)cyclobutanecarboxylic acid 
• 1503-98-6 cyclobutyl amide 
• 4426-03-3 cyclobutyl acetonitrile 
• 4426-11-3 cyclobutanecarbonitrile 
• 6540-33-6 cyclobutylacetic acid 
• 13295-53-9 cyclobutylmethyl 4-methylbenzenesulfonate 
• 5006-22-4 Cyclobutanecarbonyl chloride 
• 77500-75-5 6-Phenyl-7-(pyridine-3-carbonyl)-6,7-diaza-spiro[3.4]octane-5,8-dione 
• 77500-73-3 6-(4-Nitro-benzoyl)-7-phenyl-6,7-diaza-spiro[3.4]octane-5,8-dione 
• 77500-74-4 6-(3,5-Dinitro-benzoyl)-7-phenyl-6,7-diaza-spiro[3.4]octane-5,8-dione 

Relevant academic research and scientific papers

Synthesis of fused tricyclic amines unsubstituted at the ring-junction positions by a cascade condensation, cyclization, cycloaddition then decarbonylation strategy

Heating aldehydes that contain a protected hydroxymethyl group, a tethered alkyl chloride and a tethered alkenyl group at the α-position of the aldehyde with an amine sets up a cascade (tandem) reaction sequence involving condensation to an intermediate imine, then cyclization and formation of an intermediate azomethine ylide and then intramolecular dipolar cycloaddition. The fused tricyclic products are formed with complete or very high stereochemical control. The hydroxymethyl group was converted into an aldehyde - which could be removed to give the tricyclic amine products that are unsubstituted at the ring junction positions - or was converted into an alkene, which allowed the formation of the core ring system of the alkaloids scandine and meloscine.

Method for mildly preparing 2-azaspiro [3.3] heptane hydrochloride

The invention relates to a method for mildly preparing 2-azaspiro [3.3] heptane hydrochloride, and solves the technical problem that in historical literatures, harsh conditions of strong base sodium are needed. The synthesis method comprises the following steps: (1) reducing cyclobutane-1,1-dicarboxylic acid into dimethyl alcohol; (2) reacting the 1, 1-cyclobutane dimethyl carbinol with methanesulfonyl chloride to generate 1,1-cyclobutane dimethyl carbinol dimethyl sulfonate; (3) carrying out ring closing on the 1,1-cyclobutane dimethyl carbinol dimethyl sulfonate and the 2-nitrobenzene sulfonamide to generate 2-(2-nitrobenzenesulfonyl)-2-azaspiro [3.3] heptane; (4) enabling the 2-(2-nitrobenzenesulfonyl)-2-azaspiro [3.3] heptane to react with dodecanethiol under the action of DBU to remove the 2-nitrobenzenesulfonyl so as to generate 2-azaspiro [3.3] heptane; and (5) reacting the 2-azaspiro [3.3] heptane with BOC anhydride to generate Boc-2-azaspiro [3.3] heptane, and then performing treatment with hydrochloric acid to obtain the 2-azaspiro [3.3] heptane hydrochloride. The method is mild and easy to operate, and avoids violent conditions of removing amino protecting groups by strong base at high temperature.

Preparation method of 1, 1-cycloalkane dicarboxylic acid and derivatives thereof

The invention discloses a preparation method of 1, 1-cycloalkane dicarboxylic acid and derivatives thereof, which at least comprises the following steps of: forming a mixed system from malonic acid or derivatives thereof, dihalogenated hydrocarbon, tert-butyl alcohol salt and a solvent in a reactor; AND according to the method, the raw material conversion rate and the product selectivity are improved, and side reactions are hardly generated.

Discovery of potent c-MET inhibitors with new scaffold having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine headgroups

Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N1-(3-fluoro-4-methoxyphenyl)-N3-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy.

Ruthenium-catalyzed asymmetric hydrogenation of 3-oxoglutaric acid derivatives: A study of unconventional solvent and substituent effects

A series of 3-oxoglutaric acid derivatives have been hydrogenated in different solvents in the presence of [RuCl(benzene)(S)-SunPhos]Cl (SunPhos=(2,2,2′,2′-tetramethyl-[4,4′-bibenzo[d][1,3]dioxole] -5,5′-diyl)bis(diphenylphosphine)). Unlike simple β-keto acid derivatives, these advanced analogues can be readily hydrogenated in uncommon solvents such as THF, CH2Cl2, acetone, and dioxane with high enantioselectivities. Two possible catalytic cycles have been proposed to explain the different reactivities of these 1,3,5-tricarbonyl substrates in the tested solvents. The C-2 and C-4 substituents had notable but irregular influence on the reactivity and enantioselectivity of the reactions. More pronounced solvent effects were observed: the ee values increased from around 20 % in EtOH or THF to 90 % in acetone. Inversion of the product configuration was observed when the solvent was changed from EtOH to THF or acetone, and a mixed solvent system can lead to better enantioselectivity than a single solvent. Pronounced solvent effects: 3-Oxoglutaric acid derivatives have been hydrogenated in various solvents with high enantioselectivities (see scheme). Inversions of the product configuration were observed when the solvent was changed. Mixed solvent systems can give better enantioselectivities than a single solvent.

Selective reactions of 1,1-cycloalkanedicarboxylic acids with SF4. a route to 1,1-bis(trifluoromethyl)cycloalkanes, 1-fluoroformyl-1-(trifluoromethyl)cycloalkanes and 1-(trifluoromethyl)-1-cycloalkanecarboxylic acids

Six-, five-, four- and three-membered 1,1-cycloalkanedicarboxylic acid (2a-d) were synthesized by alkaline hydrolysis of the corresponding diesters (1a-d) and the reactions of the formers with SF4 were investigated. 1,1-Bis(trifluoromethyl)cycloalkanes (3a-d) were the products of the reactions conducted at 120-150°C while at 30°C 1-fluoroformyl-1-(trifluoromethyl)cycloalkanes (4a-d) were exclusively formed. The latter were isolated as pure compounds or converted in situ into 1-(trifluoromethyl)-1-cycloalkanecarboxylic acids (5a-d).

Spiro-Tenside und -Phospholipide: Synthese und Eigenschaften

Keywords: Micellen; Spiroverbindungen; Tenside

Octacidomycins, III: Synthetic Structural Analogues from C5-Units

The total synthesis of an isoprenoid-like analogue (2) of octacidomycin (1), a novel oligocarboxylic acid antibiotic, is described.Starting from 3 (Scheme 1) and the tetraethylester of 1,11-dibromoundecane-4,4,8,8-tetracarboxylic acid (6) as a key compound systematical fragment condensations lead to the pepntadecacarboxylic acid 12 and hence to the 1,3,7,11,15,19,23,27-heptacosane-octacarboxylic acid 2.This contains regularly connected C5- instead of C7-units and shows contracted distances between the acid groups.The newly developed synthesis yields a hitherto unknown type of oligocarboxylic acids and some useful intermediates with one or two terminal vinylic functions (13-15). - Keywords: Antibiotics, Octacidomycins, Oligocarboxylic Acids, Synthesis

General Synthesis of Methyl- and Dimethyl-cyclobutanes from Simple 1,3-Diols by Phase Transfer Catalysis

A general method is described for the preparation of methyl- and dimethyl-cyclobutanes from simple 1,3-diols.The key steps of the procedure are a phase transfer catalysed ring closure and the transformation of a carboxyl group to a methyl group.Phase transfer catalysis provides good yields in the synthesis of the cyclobutane skeleton.

Laser-Powered Decomposition of Spiroalkanes (n = 2-5)

The laser heating of spiroalkanes (n=2-5) and of their 1,1,2,2-tetradeuterated isotopomers reveals dissimilar modes of their thermal decomposition.Spiropentane decomposes into ethene and propadiene via two competing routes: the direct cleavage and the more important cleavage via intermediary methylenecyclobutane.Spirohexane decomposes through two important concurrent pathways which are the expulsions of ethene from the three-membered ring and a more feasible expulsion of ethene from the four-membered ring.Spiroheptane and spirooctane decompose by a radical-chain mechanism and afford complex mixtures of products; upon addition of propene both compounds rearrange into two cycloalkanes wherein the larger ring of the spiroalkane is preserved and substituted with ethylidene and a vinyl group.