50675-57-5

Usage

Physical state

Colorless liquid

Odor

Strong and pungent

Usage

Reagent in organic synthesis (preparation of pharmaceuticals and fine chemicals)

Building block for

Synthesis of various organic compounds (e.g. lactones and other cyclic compounds)

Reactivity

Highly reactive

Safety precautions

Potential skin and eye irritation, should be handled with caution, used in well-ventilated areas with appropriate personal protective equipment.

Upstream product

• 75885-59-5 2,2-dimethylcyclopropane-1-carboxylic acid 
• 930-50-7 [(1RS)-2,2-dimethylcyclopropyl]methanol 
• 22308-12-9 1,3-bis((p-toluenesulfonyl)oxy)-2,2-dimethylpropane 
• 28624-52-4 (R)-2,2-dimethylcyclopropanecarboxylic acid 
• 126-30-7 2,2-Dimethyl-1,3-propanediol 
• 5722-11-2 rac-2,2-dimethylcyclopropanecarbonitrile 
• 556-82-1 3-methyl-2-buten-1-ol 

Downstream Products

• 870809-25-9 4,5-bis-benzyloxy-2-methyl-benzoic acid 2-(2,2-dimethyl-cyclopropanecarbonyloxy)-3-{1,1-dimethyl-2-[(tetrahydro-furan-3-carbonyl)-amino]-ethylamino}-propyl ester 
• 1276045-05-6 (2,2-dimethyl-cyclopropyl)-[4-(3-methoxy-phenyl)-piperidin-1-yl]-methanone 
• 1428555-91-2 N-(2-aminophenyl)-2,2-dimethylcyclopropanecarboxamide 
• 1428555-92-3 1,2-bis(2,2-dimethylcyclopropyl-1-carbonylamino)benzene 

Relevant academic research and scientific papers

Industrial production of chiral intermediate of cilastatin by nitrile hydratase and amidase catalyzed one-pot, two-step biotransformation

An industrial one-pot, two-step bioprocess catalyzed by nitrile hydratase (NHase) and amidase was developed for (S)-2,2-dimethylcyclopropanecarboxamide (1), the key chiral intermediate of cilastatin. The key unit operations of the whole process including fermentative production of enzymes, biotransformation, isolation of product, and recycling of by-product were reported for the first time. The volumetric enzyme activities of NHase and amidase in 1000-L fermentor were enhanced to 351,000 and 5880 U/L, respectively. The two-step, one-pot biotransformation of rac-2,2-dimethylcyclopropanecarbonitrile (2) took full advantage of both enzymes, leading to accumulation of (S)-1 in 47% yield and 99.6% ee. (S)-1 and the by-product (R)-2,2-dimethylcyclopropanecarboxylic acid (3) were obtained with yields of 38% and 45%, respectively, by a novel macroporous resin adsorption chromatography. Moreover, the total yield of (S)-1 was further increased to 53% after one recycling of (R)-3. The new bioprocess dramatically improved process efficiency compared with the chemical route by elimination of six synthetic steps and proved to be a superior and more cost-effective approach towards (S)-1.

Synthesis of 2,3-dihydro-1H-pyrrolo[1,2-a]benzimidazoles via the cyclopropyliminium rearrangement of substituted 2-cyclopropylbenzimidazoles

2-Cyclopropylbenzimidazole derivatives with various substituents in the small ring undergo cyclopropyliminium rearrangement into 2,3- dihydropyrrolobenzimidazoles substituted at positions 1, 2 or 3. The substrates containing a functional group in position 1 of the cyclopropane ring form products substituted at position 3. Substituents at position 2 in most cases lead to the formation of a mixture of isomers. The reaction can be directed to yield one of the isomers predominantly by varying the solvent polarity.

PROCESS FOR PREPARING OPTICALLY ACTIVE CYCLOPROPANE CARBOXAMIDE AND DERIVATIVES THEREOF

The present invention relates to a process for preparing optically active cyclopropane carboxamide in a specific structure using an enzyme.

Cyclopropanecarboxylic acid amide compound and pharmaceutical use thereof

The present invention provides an NF-kappa B activation inhibitor, an inflammatory cytokine production inhibitor, a matrix metalloprotease production inhibitor, an inflammatory cell adhesion factor expression inhibitor, and an anti-inflammatory agent, an antirheumatic agent, an immuno-suppressive agent, an antiallergic agent, an antiviral agent, or a therapeutic agent for arteriosclerosis, which comprise, as the active ingredient, a cyclopropanecarboxylic acid amide compound or a pharmaceutically acceptable salt thereof effective for the treatment of inflammatory diseases.

Nitroxyl radical reactions with 4-pentenyl- and cyclopropylketenes: New routes to 5-hexenyl- and cyclopropylmethyl radicals

4-Pentenylketenes 4a and 9 and cyclopropylketenes 3a, 13, 14 (RCH=C=O) are generated by photochemical Wolff rearrangements and observed by IR as relatively long-lived species at room temperature in hydrocarbon solvents. The reactions of these ketenes with the nitroxyl radicals tetramethylpiperidinyloxyl (TEMPO, TO?) and tetramethylisoindoline-2-oxyl (TMIO, IO?) form carboxy substituted 5-hexenyl and cyclopropylmethyl radicals which are either trapped by a second nitroxyl radical or undergo rearrangements followed by trapping. The rate constant of the reaction of 4a with TEMPO was similar to that of n-BuCH=C=O (1b), while 3a was 4.3 times more reactive, indicating cyclopropyl stabilization of the incipient radical.

A new approach to the synthesis of cilastatin, an inhibitor of renal dipeptidase

A convenient preoarative synthesis of cilastatin, an inhibitor of renal dipeptidase used in drugs with the antibiotic imipenem, has been elaborated.The key intermediate in this synthesis is 2-amino-7-chloroheptanoic acid prepared by oxidative cleavage of cycloheptanone followed by bromination of 7-chloroheptanoyl chloride with subsequent amination of the 2-bromo-7-chloroheptanoic acid thus formed.All of the stages of the new synthesis are easily performed, as is the isolation of the intermediate products, and they do not require any organometallic reagents. - Key words: cilastatin, (R)-cysteine, 7-chloroheptanoic acid, 2-amino-7-chloro-2-heptenoic acid, 2,2-dimethylcyclopropanecarbonyl chloride; oxidation, bromination, amination, cyclopropanation.

Process for resolution of racemates of 2,2-dimethylcyclopropanecarboxylic acid

The enantiomers of 2,2-dimethylcyclopropanecarboxylic acid are separated by esterification with the hydroxy group of optically active mandelic acid methyl ester, crystallization of the diastereomeric esters and subsequent hydrolysis of the diastereomeric esters.

Azetidines. 5. Reaction of 1,1,3,3-Tetramethyl- and 1-Benzyl-1,3,3-trimethylazetidinium Ions with Butyllithium and Phenyllithium. Deuterium Labeling as a Mechanistic Probe

The reactions of 1,1,3,3-tetramethylazetidinium iodide (1) and 1-benzyl-1,3,3-trimethylazetidinium bromide (7) with butyllithium and with phenyllithium were studied in ether.The products from the reaction of 1 with butyllithium were 1,3,3-trimethylpyrrolidine (2), 3,3-dimethyl-4-(methylamino)-1-butene (3), 1-(dimethylamino)-2,2-dimethylheptane (4), neopentylpyrrolidine (5), and 1-(dimethylamino)-2,2-dimethylcyclopropane (6).With phenyllithium, 1 gave 2 and 1-(dimethylamino)-2,2-dimethyl-3-phenylpropane (11).With butyllithium, 7 gave 2-phenyl-1,4,4-trimethylpyrrolidine (8), 1-benzyl-3,3-dimethylpyrrolidine (9), and 1-neopentyl-2-phenylpyrrolidine (10).The reaction of phenyllithium with 7 gave only 8 and 9.Mechanistic information was obtained by labeling 1 with deuterium in three different ways: N-methyl-d3, 2,2-d2, and N-methyl-d3-2,2-d2.A primary kinetic isotope effect of 9.4 was found for the formation of 2 from 1-N-methyl-d3.When 2 was formed from 1-2,2-d2, a secondary kinetic isotope effect of 1.17 was measured.The formation of 4 from 1-2,2-d2 was accompanied by a primary kinetic isotope effect of 4.7, suggesting a carbene intermediate.Ylide carbanions involving decomposition to a carbene carbanion in the formation of 3 and an azomethine ylide in the formation of 5 and 9 are probable intermediates.It is postulated that the azomethine ylides react with ethylene formed from the reaction of butyllithium with the solvent ether by means of a concerted (4 + 2) cycloaddition reaction.A primary kinetic isotope effect of 20 was found for the formation of pentylbenzene from dibenzyldimethylammonium bromide and butyllithium.