- Trispirododecane-4,8,12-trione and Other Oligomers of Carbonylcyclopropane. The Organozinc Route
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1-Bromocyclopropanecarboxylic acid (8) and its chloride (9) were prepared from γ-butyrolactone on a 20-100-g scale.Dehalogenation of 9 with zinc-copper couple in acetonitrile gave not only the known dispiro octane-4,8-dione (3) but also the aesthetically pleasing title compound 10 and 6-cyclopropylidene-5-oxaspirohexan-4-one (11) as well as tetracyclic α-alkylidene-γ-butyrolactone 12, i.e., 3-(oxodispirooctan-4-ylidene)tetrahydro-2-furanone. "Zinc carbon enolate" 13a is considered to be an important intermediate en route to 10 in solventacetonitrile.The X-ray crystal structure of 10 shows the molecule to be nearly planar with very short distal cyclopropane carbon-carbon bonds .
- Hoffmann, H. Martin R.,Eggert, Ulrike,Walenta, Angela,Weineck, Edeltraut,Schomburg, Dietmar,et al.
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- Synthesis of optically active 2-substituted azetidine-2-carbonitriles from chiral 1-arylethylamineviaα-alkylation ofN-borane complexes
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The base-promoted α-alkylation ofN-((S)-1-arylethyl)azetidine-2-carbonitriles3viaformation of theirN-borane complexes4was investigated. For example, treatment of diastereomerically pure boraneN-((S)-1′-(4′′-methoxyphenyl)ethyl)azetidine-2-carbonitrile complex (1S,2S,1′S)-4bwith 1.2 equivalents of LDA at ?78 °C followed by 1.3 equivalents of benzyl bromide at ?78 °C and warming to room temperature produced α-benzylated (2S,1′S)-5bain 72% yield and (2R,1′S)-5bain 2% yield. A mechanism for this diastereoselective α-alkylation was proposed. Our method enables the production of optically active 2-substituted azetidine-2-carbonitriles, such as α-benzylated (S)-10aand (R)-10a, starting from commercially available (S)-(1-(4-methoxyphenyl)ethyl)amine.
- Nakanome, Nobuhiro,Tayama, Eiji
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p. 23825 - 23837
(2021/07/14)
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- Method for preparing methyl 2,4-dibromobutyrate under catalysis of brominated sulfonic acid resin
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The invention discloses a method for preparing methyl 2,4-dibromobutyrate under the catalysis of a brominated sulfonic acid resin. The method comprises the following steps: adding a brominated sulfonic acid resin catalyst with a mass fraction of 2-5% into gamma-butyrolactone; heating to 80-90 DEG C, adding a certain amount of liquid bromine in a dropwise manner, keeping the temperature at 90-100 DEG C, and reacting for 3-5 hours; cooling to room temperature, adding methanol in a dropwise manner, and reacting for 10-15 hours; filtering to remove the catalyst, washing the catalyst with a detergent, drying, and repeatedly using; and distilling the filtrate to obtain the target product. According to the invention, the catalyst is high in catalytic activity, short in reaction time and high in raw material utilization rate, and can be repeatedly used; and with the method, the damage of phosphorus-containing wastewater to the environment is avoided, the wastewater amount is less, the production cost is reduced, the post-treatment is convenient, links of extraction, water washing, drying and the like are reduced, operation is easy, product quality is high, and the environment-friendly thought is met.
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Paragraph 0024-0032
(2020/04/17)
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- Synthesis method of 5-fluoro-2-(1-bromocyclopropyl) pyridine
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The invention relates to a synthesis method of 5-fluoro-2-(1-bromocyclopropyl) pyridine. 1,4-butyrolactone, ethyl 4-bromobutyrate and 5-fluoro-2-mercaptopyridine are used as raw materials to prepare 5-fluoro-2-(1-bromocyclopropyl) pyridine through eleven steps of reaction. A synthetic route of the 5-fluoro-2-(1-bromocyclopropyl) pyridine is as follows: (as described in the specification). The invention has the advantages that the synthesis method of 5-fluoro-2-(1-bromocyclopropyl) pyridine improves the yield and provides an efficient synthesis method for the synthesis of the compound.
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Paragraph 0016; 0017; 0027; 0028; 0038; 0039
(2019/08/01)
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- Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil
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A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil. The most active analogue 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (67) afforded an in vitro IC50value of 0.03 ± 0.07 μM against acetylcholinesterase with no cytotoxicity observed (IC50of >100 μM, SH-SY5Y cell line). In comparison donepezil had an IC50of 0.05 ± 0.06 μM and an observed cytotoxicity IC50of 15.54 ± 1.12 μM. Molecular modelling showed a strong correlation between activity and in silico binding in the active site of acetylcholinesterase.
- van Greunen, Divan G.,Cordier, Werner,Nell, Margo,van der Westhuyzen, Chris,Steenkamp, Vanessa,Panayides, Jenny-Lee,Riley, Darren L.
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p. 671 - 690
(2017/02/10)
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- An efficient synthesis of 1-bromo-1-cyanocyclopropane
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An efficient process for the synthesis of 1-bromo-1-cyanocyclopropane has been developed starting from inexpensive γ-butyrolactone via bromination, cyclisation, ammoniation and dehydration reaction. The sequence proceeds in good yield.
- Xue, Feng,Li, Chang-Gong,Zhu, Yong,Lou, Tian-Jun
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p. 418 - 419
(2014/08/05)
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- SYNTHESIS OF CYCLIC AMIDINES
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The invention relates to an innovative method for synthesis of cyclic amidines. The synthesis starts from a β-, γ- or δ-lactone which is twofold brominated. After esterification of the carboxyl function, the bromine atoms are nucleophilically substituted and the corresponding diamino compound is obtained. The ring closure to the cyclic amidine is accomplished subsequently by reaction with orthoester, imidate or thioimidate. Owing to interposing additional steps for recovery of the diamino compound in enantiomerically pure form, the enantiomers of the cyclic amidines can be stereoselectively synthesized.
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Page/Page column 6
(2011/08/04)
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- NHC-Catalyzed intramolecular redox amidation for the synthesis of functionalized lactams
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A very efficient NHC-catalyzed lactamization reaction is reported. For most cases, the ring expansion reaction proceeds to cleanly furnish five- and six-membered N-Ts and N-Bn lactams, without the need for further purification. Evidence is presented suggesting a dual role for the stoichiometric base: (1) deprotonation of the triazolium precatalyst and (2) activation of the nitrogen leaving group through hydrogen bonding.
- Thai, Karen,Wang, Li,Dudding, Travis,Bilodeau, Francois,Gravel, Michel
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supporting information; experimental part
p. 5708 - 5711
(2011/03/19)
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- Preparation of enantiopure 2-acylazetidines and their reactions with chloroformates
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Enantiopure 1-phenylethylazetidine-2-carboxylates and 2-acylazetidines were prepared and reacted with chloroformates to yield α-chloro-γ-amino butyric acid esters and ketones from ring opening reaction of azetidinium ion intermediate in a completely regio- and stereoselective manner.
- Ma, Sang-ho,Yoon, Doo Ha,Ha, Hyun-Joon,Lee, Won Koo
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p. 269 - 271
(2007/10/03)
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- Enzymatic resolution of methyl N-alkyl-azetidine-2-carboxylates by Candida antarctica lipase-mediated ammoniolysis
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A facile method for the synthesis of optically active azetidine-2- carboxylic acid derivatives is presented Racemic N-alkylated azetidine esters are resolved by lipase from Candida antarctica in an ammoniolysis reaction, and both the S-amide and the R-ester are obtained with excellent stereoselectivity.
- Starmans, Wim A. J.,Doppen, Roy G.,Thijs, Lambertus,Zwanenburg, Binne
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p. 429 - 435
(2007/10/03)
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- Azetidine based ligands in boron catalyzed asymmetric
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The preparation of a new class of azetidine-based auxiliaries and their selectivity in the BBr3 catalyzed Diels-Alder reaction is described. The results are compared with a similar proline-derived ligand and a known prolinol auxiliary. Results show that selectivities are highly dependent on the dienophile and the substituent of the chiral auxiliary.
- Starmans, Wim A. J.,Walgers, Richard W.A.,Thijs, Lambertus,De Gelder, Rene,Smits, Jan M.M.,Zwanenburg, Binne
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p. 4991 - 5004
(2007/10/03)
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- 3-hydroxy-N-methylpyrrolidone and preparation thereof
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The novel compound, 3-hydroxy-N-methylpyrrolidone, is effective as a transdermal enhancer for the absorption of drugs through the skin of humans and animals. The 3-hydroxy-N-methylpyrrolidone is prepared from delta-butyrolactone which is converted to methyl 2,4-dibromobutyrate, this intermediate is reacted with methylamine to form N-methyl-2,4-dibromobutyramide, this intermediate is converted to 3-bromo-N-methyl-2-pyrrolidone by ring closure, and the 3-bromo-N-methyl-2-pyrrolidone is reacted with an alkaline earth metal carbonate or alkaline metal carbonate to form 3-hydroxy-N-methyl-2-pyrrolidone.
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- TRANSFORMATION OF N-TOSYL-2-(1,3-BUTADIENYL)AZIRIDINE INTO N-TOSYL-2-ETHENYL-3-PYRROLINE.
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1,3-Butadienylaziridines or 1,3-butadienylazetidines activated by N-tosyl group smoothly rearrange to vinylpyrroline derivatives or vinylpiperidines in the presence of a catalytic amount of Pd(PPh3)4.Triphenyltin radical induced rearrangement of title compounds is also described.
- Fugami, Keigo,Miura, Katsukiyo,Morizawa, Yoshitomi,Oshima, Koichiro,Utimoto, Kiitiro,Nozaki, Hitosi
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p. 3089 - 3098
(2007/10/02)
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- Chemical synthesis of ethylene/maleic anhydride dimer with phenylethyl end group
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A phenylethyl substituted dimer of ethylene and maleic anhydride, names 7-phenyloctane-(1,2),(5,6)-dianhydride, is chemically synthesized by (a) alkylating alkyl 2,4-dihalobutyrate with alkyl 2-cyano-3-phenylbutyrate, (b) alkylating the resulting
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