76899-07-5Relevant articles and documents
Method for removing P-methoxyphenyl protecting group on amide group
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Paragraph 0031-0057, (2021/10/27)
The invention provides a method for removing p-methoxyphenyl protecting groups on amide groups. The method comprises the steps of sequentially performing ozonation reaction and quenching treatment on a substrate and ozone in the presence of an organic solvent to obtain an oxidation intermediate, wherein an amide group in the substrate is protected by a p-methoxyphenyl group. The oxidation intermediate is subjected to a reduction reaction with carbon monoxide or a mixed gas containing carbon monoxide to remove p-methoxyphenyl. After the substrate and the ozone are subjected to ozonation reaction, the product system of the ozonation reaction is quenched, and then the quenched oxidized intermediate and carbon monoxide are subjected to a reduction reaction to remove p-methoxyphenyl groups to obtain the required amide organic matters. To the method for removing the P-methoxyphenyl protecting group on the amide group, thiourea is not needed, so that the whole process does not generate sulfur-containing wastewater, the cost is lower, and the method is more environmentally friendly.
Preparation method of azetidinone compound and preparation method 4 - acyloxy-azetidinone compound
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Paragraph 0101; 0103; 0104, (2021/11/19)
The invention provides a preparation method of a azetidinone compound and a preparation method of 4 - acyloxy-azetidinone compound. The preparation method comprises the following steps S1, an epoxy amide compound reacts with I alkali reagents to form a ring reaction, and first 1st reaction systems are obtained. Step S2: The first reaction system is subjected to hydroxyl protection reaction with a raw material including a silanization reagent and a nitrogen-containing basic organic matter to obtain second reaction systems. In step S3, second reaction system and second base reagent are subjected to isomerization reaction to obtain the azetidinone compound, wherein the epoxy amide compound has the structure shown VI, the separation process of the isomer product of the structure shown II and formula III IV is avoided, and the selectivity and yield of the azetidinone compound are improved.
Preparation method of 4AA
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Paragraph 0016; 0018; 0020-0021; 0023-0024; 0026, (2021/07/28)
The invention discloses a preparation method of 4AA. The preparation method comprises the following steps: S1, preparing a first intermediate from benzamide and a formaldehyde aqueous solution; S2, preparing a second intermediate from the first intermediate, thionyl chloride, toluene and n-heptane; S3, preparing a third intermediate from the second intermediate, methyl acetoacetate, sodium methoxide, toluene, diluted hydrochloric acid and isopropanol; S4, preparing a fourth intermediate from the third intermediate, reductase, ethyl acetate, saturated sodium bicarbonate and saturated salt water; S5, preparing a fifth intermediate from the fourth intermediate, imidazole, TBSCL and methylbenzene; S6, preparing a sixth intermediate from the fifth intermediate, ethanolamine, methanol and n-heptane; S7, preparing a seventh intermediate by using the sixth intermediate, a Grignard reagent and n-heptane; and S8, preparing 4AA from the seventh intermediate, ruthenium trichloride, potassium acetate, ethyl acetate, acetic acid and a peracetic acid solution.
Preparation method of penem antibiotic intermediate 4 - acetoxy azacyclobutanone (by machine translation)
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Paragraph 0033; 0036-0039; 0040; 0043-0046; 0054-0060, (2020/09/30)
The invention discloses a preparation method of penem antibiotic intermediate 4 - acetoxy azacyclobutanone (4 - AA), and specifically discloses a preparation method of 4 - acetoxyazacyclobutanone (4 - AA) in an organic solvent under the action of a metal catalyst and an oxidant, and has the characteristics of being economical and efficient, small in environmental pollution and high in yield 4 - 4 - AA. (by machine translation)
Synthetic method of penem drug intermediate
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, (2020/05/19)
The invention discloses a method for synthesizing biapenem medicine intermediates. The method has the advantages that the biapenem medicine intermediates 4-AA are prepared from (R)-3-polyhydroxybutyrate which is a raw material, and the raw material in the routes is inexpensive, is easily available and can be substantially purchased; the method includes simple steps, the various steps are high in yield, and reaction is simple; chiral reagents and chiral resolution are omitted, accordingly, the method is low in cost and high in yield, and reaction conditions are easily available.
Method for reduction preparation of 4-AA with inorganic reducing agent
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Paragraph 0035-0040; 0041-0046; 0047-0052; 0053-0067, (2018/03/24)
The invention discloses a method for reduction preparation of (3R,4R)-4-acetoxyl-3-[(R)-1-[(terbutyldimethylsilyl)oxy-ethyl]-2-azetidinone with an inorganic reducing agent. The inorganic reducing agent is reductive metal powder. The method includes the following steps that firstly, the inorganic reducing agent is pretreated, wherein the reductive metal powder is placed in an acidic or alkaline solution to be activated to obtain activated metal powder; secondly, ozone is introduced into a solution of a compound I for an oxidation reaction to obtain an ozonization reaction solution; thirdly, theactivated metal powder obtained in the first step is added into the ozonization reaction solution obtained in the second step for a reduction reaction, and (3R,4R)-4-acetoxyl-3-[(R)-1-[(terbutyldimethylsilyl)oxy-ethyl]-2-azetidinone is obtained, wherein the structural formula of the compound I is shown in the description. The method only needs one-step reduction, the amount of wastewater can be reduced, the content of ammonia nitrogen and sulfur in the wastewater is reduced, and the COD value of the wastewater is reduced.
The photocatalysis removing N - alkyl preparation penem pharmaceutical intermediate 4 - AA method (by machine translation)
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Paragraph 0025; 0026-0027; 0029; 0031, (2019/01/14)
A photocatalytic removing N - alkyl preparation penem pharmaceutical intermediate 4 - AA of the method, the preparation step comprises: the compound I radix Aconiti Kusnezoffii alcohol solvent of the solution to form solution; to the step (1) are added in the solution in the titanium dioxide catalyst; ultraviolet light for the irradiation step (2) of the reaction material, temperature control in the 10 °C within, then according to the thin-layer chromatography (TLC detection) to control the speed of the material point of the illumination reaction time; after the reaction, membrane filtration or centrifugal separating titanium dioxide catalyst, part of the solvent is distilled under reduced pressure recovery, then adding de-ionized water, precipitated product, then recrystallized refining to obtain the target product. L - threonine line can overcome the preparation 4 - AA final one-step in the method of removing alkyl N - the defect of complex, simple, efficient, non-metal pollution, no waste water discharge, reducing the 4 - AA synthesis cost, to reduce the environmental pressure have obvious effect; its reaction equation is as follows: (by machine translation)
Process and device for synthesizing (3R, 4R)-4-acetoxyl-3-[(R)-1-tert-butyl dimethyl silica ethyl]-2-azetidinone
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Paragraph 0050-0058, (2017/01/26)
The invention discloses a process and a device for synthesizing (3R, 4R)-4-acetoxyl-3-[(R)-1-tert-butyl dimethyl silica ethyl]-2-azetidinone. 4-AA industrial products can be synthesized by the aid of continuous reaction technologies for series connection circuit reactors. The process includes dissolving a raw material (3R, 4R)-3-[(R)-1-tert-butyl dimethyl silica ethyl]-4-acetoxyl-1-(4-methoxy phenyl)-2-azetidinone by the aid of methanol; allowing series connection circuit reaction devices to carry out oxidation deprotection on PMP protecting groups in the raw material by the aid of ozone; carrying out reduced-pressure distillation to remove the methanol and then adding water to the raw material to obtain 4-AA crude products; re-crystallizing the crude products to obtain 4-AA products. The process and the device have the advantages that the process is simple, safe in oxidation deprotection reaction operation, short in reaction time and low in running cost; the reaction yield can be greatly increased, and the mass yield of the 4-AA products is higher than 69%.
A METHOD OF PREPARATION OF (1'R,3R,4R)-4-ACETOXY-3-(1'-(TERT-BUTYLDIMETHYLSILYLOXY)ETHYL)-2-AZETIDINONE, A PRECURSOR FOR CARBAPENEM ANTIBIOTICS SYNTHESIS
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Page/Page column 12-13, (2014/07/08)
The subject of the present invention is a method of preparation of (1'R,3R,4R)-4-acetoxy-3-(1'- (tert-butyl-dimethylsilyloxy)ethyl)-2-azetidinone defined by the formula (1) which is a basic chiral building block in the synthesis of carbapenem antibiotics.
A practical preparation of the key intermediate for penems and carbapenems synthesis
Grzeszczyk, Barbara,Stecko, Sebastian,Mucha, Lukasz,Staszewska-Krajewska, Olga,Chmielewski, Marek,Furman, Bartlomiej
, p. 161 - 163 (2013/08/25)
A novel, practical and stereoselective synthesis of (3R,4R)-4-acetoxy-3-(R) -1-(t-butyldimethylsilyloxy)ethyl-2-azetidinone, a key intermediate in the preparation of β-lactam antibiotics is reported. The crucial step of the synthesis is based on the Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade between silyl protected (R)-3-butyn-2-ol and the nitrone derived from benzyl hydroxylamine and benzyl glyoxylate. The obtained adduct is subjected to debenzylation with sodium, or lithium in liquid ammonia followed by oxidation with lead tetraacetate to afford the final product.