30 results about "Phenylmagnesium bromide" patented technology

The invention relates to a preparation method for a Sacubitril intermediate. The preparation method comprises the following steps that (3R,5S)-5-(hydroxymethyl)-3-methyl-2-pyrrolidone is esterified with toluene sulfochloride or methanesulfonyl chloride to obtain (3R,5S)-5-(methyl p-toluenesulfonate)-3-methyl-2-pyrrolidinone or (3R,5S)-5-(methyl methanesulfonate)-3-methyl-2-pyrrolidinone; (3R,5S)-5-(methyl p-toluenesulfonate)-3-methyl-2-pyrrolidinone or (3R,5S)-5-(methyl methanesulfonate)-3-methyl-2-pyrrolidinone is coupled with 4-diphenylmagnesium bromide or 4-diphenylmagnesium chloride to obtain (3R,5S)-3-methyl-5-(1,1'-diphenyl-4-yl-methyl)-2-pyrrolidinone. According to the preparation method, the method is novel, the raw materials are easy to obtain, the technology is simple, and the purity and yield of the product are both very high.

The invention relates to preparation of (S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine and a preparation method of apremilast. 4-methoxy-3-ethoxy phenylmagnesium bromide is prepared from 4-methoxy-3-ethoxy bromobenzene through Grignard reaction; 4-methoxy-3-ethoxy phenylmagnesium bromide is in addition reaction with methylsulfonyl acetonitrile, and then hydrolysis and reduction are carried out, so that (R,S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine (III) is obtained; separation and filtering are carried out, so that (S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine N-acetyl-L-leucine salt (IV) is obtained; through neutralization, (S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine (II) is obtained; the compound (II) is subjected to imidization, so that apremilast (1) is obtained. The mother liquor obtained after separation is recycled and converted into a compound IV, so that discharge of waste liquid is reduced, environment friendliness is realized and the cost is reduced.

The present invention is one kind of 2-substituted rubrene compound as shown and its synthesis process. The synthesis process includes the first synthesis of 2-formoxyl rubrene, and the subsequent oxidation, reduction and condensation with 2-formoxyl rubrene to obtain other 2-substituted rubrene compound. The synthesis process of 2-formoxyl rubrene under protection of inert gas includes the first reaction of 2-formoxyl -6, 11-diphenyl-5, 12-tetracene quinine material with glycol and catalyst at 120-160 deg.c; the subsequent reflux reaction with phenyl magnesium bromide and anhydrous tetrafuran; and final reflux reaction with iron powder and glacial acetic acid under heliophobic condition to obtain 2-formoxyl rubrene. The 2-substituted rubrene compound of the present invention as new type of red fluorescent material has high fluorescence quantum efficiency and may be used as the luminous material in electroluminescent device.

The invention discloses a preparation method of 1,1-diphenylethylene shown in a formula (V). The method comprises the steps of firstly carrying out reaction on bromobenzene and magnesium chips in anhydrous 2-methyltetrahydrofuran to obtain a phenylmagnesium bromide Grignard reagent, and then dripping acetophenone into the phenylmagnesium bromide Grignard reagent to react, so as to generate 1,1-diphenylethanol; finally, dewatering 1,1-diphenylethanol in the presence of a sulfoacid functional ionic liquid catalyst, so as to obtain 1,1-diphenylethylene shown in the formula (V). The preparation method disclosed by the invention is short in reaction step, mild in condition, simple and convenient to operate, high in product yield, low in production cost, friendly to environment, and applicable to industrial production.

The invention discloses a preparation method of ulipristal acetate and an intermediate thereof, and belongs to the field of pharmaceutical synthesis. The preparation method of the ulipristal acetate comprises the following steps: by taking 3,3-(ethylenedioxy)-19-methylestra-5(10),9(11)-diene-3,17-diketone as raw material, enabling the raw material to react with sodium acetylide or potassium acetylide to obtain a compound III, carrying out high-selectivity epoxidation by oxide to obtain a compound IV, subsequently enabling the compound IV to react with 4-(N,N-dimethyl amino) phenyl magnesium bromide Grignard reagent to obtain a compound V, then enabling the compound V to react with phenyl sulfonic acid chloride to obtain a compound VI, enabling the compound VI to respectively react with sodium methoxide and trimethyl phosphate to obtain a compound VII, hydrolyzing and removing a protection group to obtain a compound VIII, finally carrying out acetylation reaction to obtain the ulipristal acetate, wherein the reaction formulae are as shown in the description. The method is short in synthetic route, mild in reaction conditions, high in yield and purity of products, low in cost, stable and controllable in quality, and is suitable for industrial production.

The invention discloses a synthesis method of a 9,9'-spirobifluorene derivative, and belongs to the field of organic chemical synthesis. The method comprises the steps that 2-bromochlorobenzene as a raw material acts with phenylmagnesium bromide and then reacts with bromofluorenone at 50-100 DEG C in a methyltetrahydrofuran solvent, hydrolysis and filtration are performed, solid performs closed-loop synthesis under acid catalysis to produce bromo-9,9'-spirobifluorene, and bromo-9,9'-spirobifluorene reacts with lithium diphenylphosphide to synthesize the 9,9'-spirobifluorene diphenylphosphine derivative. The synthesis method is simple in process; raw materials are low in price and easy to obtain; the production cost of series products is obviously lowered during synthesis; and the application of the fluorene derivative in design and synthesis of organic photoelectric materials as an intermediate is extended.

The invention discloses a preparing method of 3-alkoxy phenylcarbinol, comprising the steps: (1) dissolving 3-bromobenzene alkyl ether into a solvent, thus generating a Grignard reagent (3-alkoxy) phenyl magnesium bromide with Mg under the action of an initiator; (2) adding paraformaldehyde into the Grignard reagent at 50-85 DEG C to generate a substitution product; (3) performing acid hydrolyzing on the substitution product to obtain 3-alkoxy phenylcarbinol. Raw materials adopted in the invention are lower in price, the preparing method is mild in reaction conditions, only post-treatment of one time is required after three steps of reaction, and operation time is short; the purity of the obtained 3-alkoxy phenylcarbinol is high and completely accords with the requirements on use as a medicine intermediate.

The invention discloses a large-scale preparation method of a chiral sulfinamide monophosphine ligand. The method includes condensing chiral sulfinamide and 2-(diphenylphosphino)benzaldehyde which areadopted as raw materials to obtain an intermediate that is chiral sulfinyl imide, and carrying out a nucleophilic addition reaction with a phenylmagnesium bromide reagent to generate the chiral sulfinamide monophosphine ligand. The intermediate imine product and a final product chiral sulfinamide monophosphine ligand are purified by adopting a crystallization method, and column chromatography isnot needed. The method has the characteristics of cheap and accessible raw materials, simple synthesis steps, large-scale synthesis and preparation, a specific three-dimensional structure of the product and the like. The method is mild in condition, and is of important significance for future process and commercialization development of chiral sulfinamide monophosphine ligand products.

The invention discloses a method for synthesizing an AHU377 calcium salt. The method comprises the following steps: reacting 4-bromo-D-phenylalanine with thionyl chloride, reacting obtained methyl 4-bromo-D-phenylalaninate hydrochloride with BOC acid anhydride, reacting the obtained reaction product with phenylmagnesium bromide to obtain N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methylester, reacting the N-tert-butyloxycarbonyl-amino-4,4-biphenyl-R-alanine methyl ester with sodium borohydride, reacting the obtained reaction product with ethyl 2-(triphenylphosphoranylidene)propionate to obtain ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoate, reacting the ethyl (4R)-5-[1,1'-biphenyl]-4-yl-4-[[tert-butoxycarbonyl]amino]-2-methyl-2-pentenoatewith lithium hydroxide, performing catalytic hydrogenation, reacting the obtained catalytic hydrogenation product with thionyl chloride to obtain ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, and stirring and reacting the ethyl (2R, 4S)-5- ([1,1-biphenyl)-4-amino-2-methylpentenoate hydrochloride, calcium chloride and succinic anhydride to obtain the target product.The method has the advantages of simple steps, mild reaction conditions, high purity and high yield.

The invention discloses a synthesis method of ulipristal acetate. The synthesis method comprises the following steps: 1), producing a compound VI from gestadienol under the action of ethylene glycol,p-toluenesulfonic acid and trimethyl orthoformate; 2), oxidizing the compound VI by using hydrogen peroxide to obtain a compound VII; 3), preforming a reaction on the compound VII and a 4-(N, N-dimethylamino) phenylmagnesium bromide Grignard reagent to obtain a compound VIII; 4), hydrolyzing a compound VIII to obtain a compound XI; 5), preforming a reaction on the compound XI, glacial acetic acidand acetic anhydride under the catalytic action of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 4-dimethylaminopyridine and iron perchlorate to obtain the ulipristal acetate. In the synthesis method, reaction conditions for obtaining the ulipristal acetate from ulipristal are relatively mild, demethylated ulipristal or ulipristal oxynitride is unlikely to produce, and the production process is more controllable.

The invention provides a preparation method for p-phenylbutoxybenzoic acid, belonging to the field of organic synthesis. According to the invention, palladium-based catalytic coupling is adopted, andthe Grignard reaction and the Friedel-Craft reaction are avoided, thereby avoiding the production of blue-green copper ion wastewater and generation of a large amount of acidic wastewater due to usageof aluminum trichloride; the preparation method of the invention is friendly to environment, simple in synthesis route and high in the yield of each step; and halogeno-benzene is used for replacing more expensive phenylmagnesium bromide and used as a starting material, so the preparation cost of p-phenylbutoxybenzoic acid is lowered. The p-phenylbutoxybenzoic acid obtained in the invention has good crystal form, high purity and good solubility. The data of embodiments of the invention show that the total yield of p-phenylbutoxybenzoic acid prepared in the invention is 60% or above, and the HPLC purity of p-phenylbutoxybenzoic acid is 99.9% or above.

The invention discloses one-pot synthesis method for a substituted indane compound. The method comprises the following steps: slowly and dropwise adding a mixed solution dissolved with far-end double-bond aryl halide and PEPPSI into a mixed solution of a phenylmagnesium bromide Grignard reagent and iodoisopropane, and stirring the reaction solution at a room temperature for 5-15 minutes; and quenching the reaction solution with a saturated NH4Cl solution, conducting extracting with ethyl acetate, washing the organic phase with saturated edible salt water, carrying out drying with anhydrous sodium sulfate, concentrating the organic phase, and carrying out column chromatography separation to obtain the substituted indane compound. According to the method, the transition metal salt PEPPSI andiodoisopropane in a catalytic system are commercial products; a catalytic reaction is conducted under mild conditions and is easy to operate; the related reaction can synthesize the target compound by using a one-pot process, so material resources and human resources can be further saved, and the social necessary labor time for synthesizing the target compound is shortened; and the cyclized coupling product synthesized by using the method has potential pharmaceutical activity and also has important reference value for the industry.

The invention discloses a preparation method of pridinol mesylate. The preparation method comprises the following steps: carrying out reaction on methyl acrylate and piperidine to obtain methyl 3-(1-piperidyl) propionate, carrying out reaction on methyl 3-(1-piperidyl) propionate and phenyl magnesium bromide (as a Grignard reagent) to obtain pridinol, and forming a salt by pridinol and methanesulfonic acid in a solvent such as an ether solvent to obtain pridinol mesylate as a final product. The process route is simple in synthetic steps, is short in reaction route, is high in yield and is economical and practical.

The invention discloses a novel method for preparing penehyclidine hydrochloride, which comprises the following steps: taking quinuclidin-3-ol as a raw material, carrying out chloromethylation on the quinuclidin-3-ol, trioxymethylene and hydrochloric acid to obtain an intermediate 1, preparing the intermediate 1 into a Grignard reagent to obtain an intermediate 2, carrying out addition reaction on the intermediate 2 and N-methoxyl-N-methylcyclopentanecarboxamide to obtain an intermediate 3, and preparing the intermediate 3 into the penehyclidine hydrochloride. And reacting the intermediate 3 with a phenylmagnesium bromide Grignard reagent to obtain penehyclidine, and salifying the penehyclidine through hydrochloric acid to obtain the penehyclidine hydrochloride. According to the method, the reaction conditions are simple, the steps 2-4 are a one-pot shrinkage reaction, the operation is simple and easy to implement, a large amount of operations such as distillation and crystallization are omitted, and the emission of volatile organic gases (VOCs) and organic waste liquid is greatly reduced; the preparation raw materials are cheap and easy to obtain, the production cost is low, and industrial production prospects are achieved.

The invention relates to a synthesis technology of an insecticidal pesticide intermediate, and in particular relates to a synthesis method of a benzfuryl alcohol compound. The preparation method is characterized by comprising the following steps: (1) deprotonating acetone at the temperature of-50 to-70 DEG C, and reacting the deprotonated acetone with oxetanone to obtain a 3-oxetanol derivative; (2) carrying out ring-opening reaction on the product obtained in the step (1) under the action of acid to obtain 2-methyl-3-furanol; (3) protecting hydroxyl in the product obtained in the step (2) by using chlorosilane; (4) brominating methyl in the product obtained in the step (3); (5) carrying out substitution reaction on the product obtained in the step (4) and phenyl lithium or phenyl magnesium bromide to obtain a benzfuryl silyl ether compound; and (6) carrying out silicon-based deprotection on the benzfuryl silyl ether obtained in the step (5) by using fluoride to obtain the benzfuryl alcohol compound. The synthesis method of the benzyl furofuryl alcohol is convenient to operate, the raw materials are simple and easy to obtain, and the overall yield is obviously improved compared with the prior art.