81results about How to "Reasonable reaction process design" patented technology

The invention relates to a synthesis method of tert-butyl-1, 7-diazaspiro [3.5] nonane-1-formate, and mainly solves the technical problem that no suitable industrial synthesis method exists at present. The method comprises the following seven steps: 1, reacting a compound 1 with ethyl malonate added into a solvent ethanol to obtain a compound 2; 2, reacting the compound 2 with lithium borohydridein tetrahydrofuran to obtain a compound 3; 3, reacting the compound 3 with p-toluenesulfonyl chloride in dichloromethane to obtain a compound 4; 4, adding cesium carbonate into the compound 4 in acetonitrile serving as a solvent for cyclization to obtain a compound 5; 5, adding magnesium chips into the compound 5 in methanol serving as a solvent for reduction to obtain a compound 6, 6, reacting the compound 6 with Boc anhydride in dichloromethane to obtain a compound 7, and 7, reacting the compound 7 with palladium on carbon in methanol to obtain a final compound 8.

The invention relates to a synthesis method of 8-oxo-5-oxa-2-diazaspiro [3.5] nonane-2-tert-butyl formate, and mainly solves the technical problem that no industrial method suitable for industrial synthesis exists in the prior art. The synthesis method comprises three steps that 1, a compound 1, a compound 2 and TMEDA react in a solvent of tetrahydrofuran to obtain a compound 3; 2, the compound 3 is subjected to intramolecularly ring closing to obtain a compound 4 under the gathering effects of chlorine tosylate by using n-butyllithium as the alkali; 3, the compound 4 and ozone react to obtain a final compound 5. A reaction formula is shown in the specification.

The invention relates to a synthesis method of tert-butyl-8-oxo-2,6,9-triazaspiro[4.5]decane-2-formylate. The technical problem that an appropriate industrial synthesis method is inexistent at presentis mainly solved. The synthesis method is divided into two steps: the first step, adding triethylamine in a methanol solution dissolved with a compound 1 and amino ethyl acetate hydrochloride, and then dropwise adding tetraisopropyl titanate in the reaction solution, after completing the dropwise adding, reacting the mixed system for 12 h at 25 DEG C; adding trimethylsilyl cyanide in the reactionsystem at 25 DEG C, and then reacting for 12 h at 25 DEG C, performing post-treatment to obtain a compound 2; and the second step, adding the compound 2, nickel and ammonia water in the methanol solution, and performing hydrogenation to obtain the final compound.

The invention relates to a synthesis method of a compound of 7-hydroxymethyl-2,5-diazaspiro [3,4] octane-2-dimethylethylester, and mainly solves the technical problem that no industrial method suitable for industrial synthesis exists in the prior art. A compound 1 and triethyl-phosphite are used as raw materials for synthesizing and obtaining the final compound through eight steps. A reaction formula is shown in the specification.

The present invention relates to a 6-(tert-butoxycarbonyl) octahydro-furo [2,3-c] pyridine-4-carboxylic acid synthetic method and mainly solves a technical problem that currently no suitable industrial synthetic method exists. The synthetic method comprises ten steps as follows: firstly a compound 1 is subjected to a reductive amination with a furfural to obtain a compound 2; then the compound 2 is subjected to alkylation to produce a compound 3; the compound 3 is hydrolyzed to obtain a hydrolyzate 4; the hydrolyzate 4 is subjected to an intramolecular Friedel-Crafts reaction to obtain a compound 5; the compound 5 is subjected to a hydrogenation reduction to obtain a compound 6; a trifluoromethanesulfonyl is bond to a ketone group of the compound 6 to obtain a compound 7; a carbonyl group inserted to the compound 7 to obtain a compound 8; the compound 8 is subjected to a double bond hydrogenation reduction to obtain a compound 9; the compound 9 is subjected to ethoxycarbonyl removing by a strong acid; and the ethoxycarbonyl removed compound 9 is reacted with a Boc anhydride to obtain a final compound 11. The reaction formulas are described as follows.

The invention relates to a synthesis method of cis5-tert-butyl-3A-methyl-tetrahydro 1H-furan[3,4 c] pyrrole 3A,5(3H) dicarboxylic ester. The method mainly solves the technical problem that no proper industrial synthesis method exists in the prior art. The method comprises five steps that: 1, a compound 1 uses sodium borohydride as a reducing agent to react in an ethanol solvent to obtain a compound 2; 2, the compound 2 uses tetrahydrofuran as a solvent to obtain a compound 3 under the effects of triphenylphosphine and diisopropyl azodicarboxylate; 3, the compound 3 and the N-methoxymethyl-N-(trimethylsilyl) benzylamine use dichloromethane as a solvent to obtain a compound 4 through room temperature reduction under the action of trifluoroacetic acid; 4, the compound 4 and thionyl chloride react under the methanol backflow condition to obtain a compound 5; 5, the compound 5 uses palladium hydroxide catalysts and Boc anhydride auxiliary agents to obtain a final compound 6 through catalytic hydrogenation reaction.

The invention relates to a synthesis method of 8-(tert-butyloxycarbonyl)-6, 7, 8, 9-tetrahydro-5-hydro-imidazole[1, 5-a][1, 4]diaza-6-carboxylic acid. In the method, 8-(tert-butyloxycarbonyl)-6, 7, 8, 9-tetrahydro-5-hydro-imidazole[1, 5-a][1, 4]diaza-6-carboxylic acid is synthesized from easily-available 1-hydroimidazole-4, 5-dicarboxylic acid as the raw material by ten steps. And 8-(tert-butyloxycarbonyl)-6, 7, 8, 9-tetrahydro-5-hydro-imidazole[1, 5-a][1, 4]diaza-6-carboxylic acid is a useful organic synthesis intermediate.

The invention relates to a preparation method of 7-tert-butyl 3-ethyl 8-methyl-5,6 dihydrotriazolopyrazine 3,7(8H) phthalate ester and mainly solves the technical problems that at present, a compoundis not suitable for an industrial preparation method. The preparation method comprises the following steps: taking 2-chloro-3-methylpyrazine as a starting raw material and preparing the 7-tert-butyl-3-ethyl-8-methyl-5,6-dihydro-[1,2,4]triazol[4,3-a]pyrazine-3,7(8H)-phthalate ester through three-step reaction. A reaction formula is shown in the Specification. The 7-tert-butyl-3-ethyl-8-methyl-5,6-dihydro-[1,2,4]triazol[4,3-a]pyrazine-3,7(8H)-phthalate ester obtained by the preparation method provided by the invention is a useful intermediate or a product for synthesis of multiple drugs.

The invention relates to a synthesis method of spiro[2.5]octane-5-carboxylic acid, and is used for solving the technical problems of the existing method that the synthesis operation is difficult and the raw materials are expensive. A conventional industrial raw material 1,3-cyclohexanedione is used as a start raw material which reacts with methanol through the catalysis of concentrated sulfuric acid to obtain 3-methoxy-cyclohexenone; 3-methoxy-cyclohexenone is cyclized with an ethyl Grignard reagent in the presence of Lewis acid to obtain 5-methoxyspiro[2.5]oct-4-ene; in the presence of p-toluenesulfonic acid, 5-methoxyspiro[2.5]oct-4-ene is stirred in tert-methyl ether at room temperature to obtain spiro[2.5]oct-5-one; and in the presence of alkali and ethanol, spiro[2.5]oct-5-one reacts with p-tosyl isonitrile at 50 DEG C by taking dimethoxyethane as a solvent to obtain spirao[2.5]oct-5-nitrile; and reflux hydrolysis is performed in an alkaline condition to obtain spiro[2.5]octane-5-carboxylic acid.

The invention relates to a preparation method of 4-methyl formate-2-oxo-1,8-diazaspiro[4.5]decane-8-tert-Butyl formate and mainly solves the technical problem that there is no method suitable for industrial synthesis so far. The preparation method comprises the following two steps: Step 1, a compound 1 and dimethyl maleate react under the action of tetrabutylammonium iodide and potassium fluoridewith dimethyl sulfoxide used as a solvent to generate a compound 2; and Step 2, the compound 2 is subjected to raney nickel/H2 catalytic hydrogenation in methanol used as a solvent to obtain a compound 3, namely 4-methyl formate-2-oxo-1,8-diazaspiro[4.5]decane-8-tert-Butyl formate. The reaction equation is as shown in the specification.

The invention relates to the chemical synthesis field, and concretely relates to a synthetic method of 6-oxo-2-azaspiro[3,3]heptane-2-t-butyl carboxylate. The synthetic method is characterized in that the synthetic method comprises the following steps: 1, reducing a raw material compound (14) with lithium aluminum hydride; 2, selecting Ts (toluene sulfonyl) protection; 3, carrying out ring closure on the substance obtained in step 2 and o-nitrobenzenesulfonamide under the action of potash to obtain a compound (19); 4, reacting the compound (19) with thiophenol in a solvent DMF (dimethylformamide) under the action of potash to obtain a compound (20); and 5, generating a ketone under acidic conditions, and reacting the ketone with BOC2O (di-tert-butyl dicarbonate) under alkaline conditions to obtain 6-oxo-2-azaspiro[3,3]heptane-2-t-butyl carboxylate. The preparation method of the invention, which allows the yield to be high, the whole yield to reach 41% and conditions to be mild, is a synthetic method with large scale preparation values.

The invention relates to a method for synthesizing (3aS, 6aR)-5-(tert-butoxycarbonyl)-2-oxooctahydropyrrolo[3, 4-b]pyrrole-3a-carboxylic acid, and mainly solves a technical problem of absence of a method suitable for industrial synthesis at present. The method provided by the invention comprises the following four steps: step one, dissolving a compound 1, ethyl bromoacetate and tetrabutylammoniumfluoride in tetrahydrofuran to obtain a compound 2; step two, dissolving the compound 2, hydroxylamine hydrochloride and sodium bicarbonate in a mixed solvent of tetrahydrofuran and ethanol to obtaina compound 3; step three, adding the compound 3, Raney nickel and ammonia water into ethanol, filtering and spin-drying to obtain a compound 4 after finishing reaction; and step four, adding the compound 4 and sodium ethoxide into ethanol, performing reflux reaction to obtain a white solid compound 5, namely, (3aS, 6aR)-5-(tert-butoxycarbonyl)-2-oxooctahydropyrrolo[3, 4-b]pyrrole-3a-carboxylic acid.

The invention provides a process synthesis method of 1,7-diazaspiro[3.5]nonane-7-tert-butyl formate. The synthesis method comprises the following five steps: 1, reacting a compound 1 with a bromine compound 2 and ammonium acetate by a one-pot method to obtain a compound 2; 2, reducing a compound 3 by using lithium borohydride to obtain a compound 4; 3, using triethylamine is used as alkali, and reacting the compound 4 with p-toluene sulfonyl chloride to generate a compound 5; 4, under the catalysis of potassium iodide, taking cesium carbonate as alkali, and carrying out ring closing on the compound 5 to generate a compound 6; and 5, under the action of magnesium chips, removing p-toluene sulfonyl from the compound 6 to obtain a compound 7. The method mainly solves the technical problem that no method suitable for industrial synthesis exists at present, and has the advantages that raw materials are easy to obtain, the total yield is high, and the method is suitable for industrial production.

The invention relates to a preparation method of tert-butyl-1-oxo-6-oxa-9-azaspiro[4.5]decane-9-carboxylate, and mainly solves the technical problem that no suitable industrial synthesis method existsat present. The preparation method comprises the following five steps: step 1, dissolving a compound 1 in tetrahydrofuran, dropwise adding lithium hexamethyldisilazide under protection of nitrogen, then adding bromopentene, and after the reaction is finished, treating the obtained crude product compound 2; step 2, adding potassium permanganate into a mixed solvent of the compound 2, sodium periodate and acetone in batches, and carrying out treatment after a reaction is completed to obtain a compound 3; step 3, dissolving the compound 3 and cesium carbonate in acetonitrile, dropwise adding iodomethane, and carrying out treatment after a reaction is completed to obtain a compound 4; step 4, sequentially adding the compound 4 and potassium tert-butoxide into tetrahydrofuran, and carrying outtreatment after a reaction is completed to obtain a compound 5; and step 5, adding the compound 5 into hydrochloric acid, adjusting alkalinity after a reaction is completed, then adding Boc anhydride, carrying out stirring for a reaction, and carrying out treatment to obtain a compound 6.

The invention relates to a synthetic method of 5-(boc t-butoxycarbonyl)-1-methyl-4,5,6,7-tetrahydro-1H-imidazo-[4,5-c]pyridine-7-carboxylic acid, and mainly aims to solve the technical problem that a method suitable for industrial synthesis is unavailable at present. The synthetic method comprises the four steps: I, performing a carbonyl inserting reaction under the catalysis of palladium to obtain a compound 2; II, hydrogenating the compound 2 under the catalysis of strong hydrochloric acid to obtain a compound 3; III, reacting the compound 3 with BOC acid anhydride under a triethylamine alkaline condition to obtain a compound 4; IV, hydrolyzing the compound 4 with sodium hydroxide to obtain a compound 5. The chemical reaction formula is shown in the description.

The invention relates to a synthesis method of tert-butoxycarbonyl-1-(benzyl)-3-iodo-[1,8]diazaspiro[4,5]heptane-8-carboxylate, and mainly solve the technical problem that no synthesis method suitablefor industrialization exists at present. The method is divided into three steps: the first step, a compound 1 and benzylamine are reacted to obtain a compound 2 in the solvent toluene under the action of potassium carbonate; the second step, the compound 2 and allyl magnesium bromide are reacted to obtain a compound 3 in toluene; and the third step, the compound 3 and iodine are reacted to obtaina final compound 4 in the solvent acetonitrile under the action of sodium bicarbonate. The reaction formula is as shown in the specification.

The invention relates to a preparation method of tert-butyl-8-oxo-2-azaspiro-[4.5] decane-2-formate, and mainly aims to solve the technical problems of high raw material cost, difficulty in reaction control, inconvenience in experimental operation and the like in an existing synthesis process. According to the method, tert-butyl-8-oxo-2-azaspiro-[4.5] decane-2-formate is prepared from cheap and easily available 1, 4-dioxaspiro [4.5] decane-8-one as an initial raw material through four steps of reaction. The reaction formula is shown in the specification. The tert-butyl-8-oxo-2-azaspiro-[4.5] decane-2-formate obtained in the invention is a useful intermediate or product synthesized from a plurality of medicines.

The invention relates to a synthesis method of (6S,7S)-9-t-butyloxycarbonyl-7-(trifluoromethyl)-2,9-diazaspiro[5.5]undecane, aiming at mainly solving the technical problem that a suitable industrial synthesis method does not exist at present. The synthesis method is divided into six steps as follows: firstly, taking a compound 1 and oxalyl chloride to react to obtain a compound 2; then, hydrogenating by palladium on carbon to generate a compound 3; taking the compound 3 to react with BOC (Butyloxycarbonyl) acid anhydride under an alkaline condition to obtain a compound 4; taking the compound 4 and acrylonitrile to be subjected to alkylation reaction under the action of sodium ethoxide to obtain a compound 5; carrying out reduction and ring closure on the compound 5 under the action of Raney nickel to obtain a compound 6; reducing the compound 6 with borane-dimethylsulfide to obtain a final compound 7, wherein a reaction formula is shown in the description.

The invention discloses a preparation method of 2-(2-(tert-butyloxycarbonyl)-2-azaspiro [3.4] octane-5-yl) acetic acid. The preparation method comprises the following steps: dissolving a compound 1 and a compound 2 in 2-methyl tetrahydrofuran, dropwise adding lithium bis (trimethylsilyl) amide, and reacting to obtain a compound 3; dissolving the compound 3 into acetone, and reacting with sodium iodide to obtain a compound 4; dissolving the compound 4 in 2-methyl tetrahydrofuran, dropwise adding n-butyllithium, and reacting to obtain a compound 5; dissolving the compound 5 into 2-methyl tetrahydrofuran, then adding a compound 6, alkali and 1, 8-diazabicyclo undecene-7-ene, and reacting at room temperature to obtain a compound 7; dissolving the compound 7 into ethyl acetate, adding a catalyst, and reacting in hydrogen to obtain a compound 8; dissolving the compound 8 into tetrahydrofuran and water, adding alkali for hydrolysis to obtain a final compound 9, and continuously optimizing thestructure of a spiro compound to obtain the synthesis method suitable for industrial production.