178306-49-5

Usage

Uses

Used in Analytical Chemistry:
(R)-2-hydroxy-3-methoxy-3,3-diphenylpropanoic acid is used as a chiral reference compound for analytical studies. It is particularly valuable in chiral discrimination of α-functionalized acids, which is crucial for understanding the stereochemistry and biological activity of various compounds.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, (R)-2-hydroxy-3-methoxy-3,3-diphenylpropanoic acid is utilized as an impurity standard for Ambrisentan Hydroxy Acid. This application is essential for quality control and assurance processes, ensuring the purity and efficacy of the final drug product. By using (R)-2-hydroxy-3-methoxy-3,3-diphenylpropanoic acid as an impurity standard, researchers and manufacturers can accurately assess the presence and concentration of impurities, thereby maintaining the safety and effectiveness of pharmaceuticals.

Upstream product

• 178306-52-0 (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid 
• 119-61-9 benzophenone 
• 124-41-4 sodium methylate 
• 96-34-4 methyl chloroacetate 
• 178306-47-3 2-hydroxy-3-methoxy-3,3-diphenylpropionicacid methyl ester 
• 67-56-1 methanol 
• 53884-87-0 3,3-diphenyl-2,3-epoxypropionic acid 
• 72-18-4 L-valine 
• 178306-51-9 (S)-2-hydroxy-3-methoxy-3,3-diphenyl propionic acid 
• 1492-24-6 L-2-aminobutyric acid 
• 76527-25-8 3,3-diphenyloxirane-2-carboxylic acid methyl ester 
• 177036-94-1 ambrisentan 
• 42142-15-4 1-(4-nitro-phenyl)-ethylamine 
• 4187-53-5 (S)-1-(p-nitrophenyl)ethylamine 

Downstream Products

• 178306-52-0 (S)-2-hydroxy-3-methoxy-3,3-diphenylpropionic acid 
• 1431363-04-0 methyl 3-methoxy-2-oxo-3,3-diphenylpropionate 
• 178306-47-3 2-hydroxy-3-methoxy-3,3-diphenylpropionicacid methyl ester 
• 1240470-84-1 (S)-methyl-2-(4,6-dimethylpyrimidin-2-yloxy)-3-methoxy-3,3-diphenylpropionate 
• 177036-94-1 ambrisentan 
• 178306-46-2 (.S)-2-(4,6-dimethoxypyrimidin-2-yloxy)-3-methoxy-3,3-diphenyl propionic acid 

Relevant academic research and scientific papers

Preparation method of (S)-2-hydroxy-3-methoxy-3, 3-diphenyl propionic acid

The invention discloses a preparation method of (S)-2-hydroxy-3-methoxy-3, 3-diphenyl propionic acid, and relates to the field of drug synthesis. The method comprises the following steps: resolving (RS)-2-hydroxy-3-methoxy-3, 3-diphenyl propionic acid by using a resolution reagent (1S, 2S)-2-amino-1-(4-nitrophenyl) propane-1, 3-diol, carrying out cooling crystallization, collecting solids to obtain a salt of an S-configuration diastereoisomer, adding water into the salt of the S-configuration diastereoisomer to dissolve the salt again, carrying out acidifying, and carrying out extracting, drying, concentrating and recrystallizing to obtain high-optical purity (S)-2-hydroxyl-3-methoxyl-3-diphenyl propionic acid. According to the method, the resolution reagent which is cheap, easy to obtainand good in safety is used, the mass yield is 45% or above while the cost is reduced, the method can be amplified to large-scale industrial production, and the method has very good industrial prospects.

Synthesis method of 2-hydroxy-3-methoxy-3, 3-diphenyl propionic acid

The invention relates to a synthetic method of 2-hydroxy-3-methoxy-3, 3-diphenyl propionic acid. The invention relates to a preparation method of an ambrisentan key intermediate 2-hydroxy-3-methoxy-3,3-diphenyl propionic acid. According to the preparation

Preparation method ambrisentan key intermediate

The invention relates to a preparation method ambrisentan key intermediate (S)-2-hydroxy-3-methoxy-3, 3-diphenylpropanoic acid. According to the preparation method, 2-hydroxy-3-methoxy-3, 3-diphenylpropanoic acid containing R configuration is subjected to hydroxy protection and hydroxy substitution reaction to change the R configuration into S configuration. The preparation method is capable of realizing high efficiency configuration change, recycling of (R)-2-hydroxy-3-methoxy-3, 3-diphenylpropanoic acid after splitting, improving atom economical performance, and reducing ambrisentan cost greatly.

METHOD FOR PRODUCING (S)-2-HYDROXYPROPANOIC ACID DERIVATIVE

PROBLEM TO BE SOLVED: To provide a method for producing an (S)-2-hydroxypropanoic acid derivative and ambrisentan having high optical purity in an industrially advantageous manner. SOLUTION: There is provided a method for producing an (S)-2-hydroxypropanoic acid derivative represented by the formula (1a) by reacting an (RS)-2-hydroxypropanoic acid derivative represented by the formula (1) with (S)-(+)-1,2,3,4-tetrahydro-1-naphthylamine to form a diastereomer salt, followed by desalting. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT

2 - Hydroxy - 3 - methoxy - 3, 3 - diphenyl-propionic acid racemate resolution method

The invention relates to a resolution method of 2-hydroxy-3-methoxy-3,3-dibenzylpropionic acid racemate. The method comprises the following steps: reacting racemic acid with an optical alkali, and separating non-enantiomeric salts of acid and alkali. L-proline methyl ester hydrochloride and R-(+)-alpha-phenylethylamine are used as optically active alkalis. Highly pure target compounds can be obtained in a high yield mode by using an efficient and cheap resolution reagent, and the method has good reappearance in industrial production and has a wide industrial application prospect.

Method for preparing 2-hydroxy-3-methoxy-3,3,-diphenyl propionate racemate

The invention provides a method for preparing racemate 2-hydroxy-3-methoxy-3,3,-diphenyl propionate. The method comprises the following steps: 1) dissolving R-2-hydroxy-3-methoxy-3,3,-diphenyl propionate-L-proline methylester salt in a mixed solvent to obtain a solution; 2) adding a first acid solid or a solution into the solution of the step 1), and performing backflowing; 3) after the reaction is completed, adding a solution of a second acid, performing liquid separation, and collecting an organic phase; 4) concentrating the organic phase, dissolving a residue obtained after desolvation into ethanol or methanol, adding a hydroxide solution, separating out racemate 2-hydroxy-3-methoxy-3,3,-diphenyl propionate, drying, and filtering, thereby obtaining the racemate 2-hydroxy-3-methoxy-3,3,-diphenyl propionate. The invention further provides a process for preparing S-2-hydroxy-3-methoxy-3,3,-diphenyl propionate. The yield can be increased to about 40% from 30%, meanwhile wastes can be reduced, and good economic benefits and social benefits can be achieved.

Process for Preparing Ambrisentan

The present invention relates to a method of preparing high purity ambrisentan in a cost-effective and efficient way, and a novel intermediate product used for the method. According to the present invention, optical resolution of 2-hydroxy-3-methoxy-3,3-diphenylpropionic acid can be cost-effectively and efficiently performed using L-prolinamide, and thus crystalline ambrisentan having 99.9% or more of purity and optical purity can be prepared on an industrial scale using the same.COPYRIGHT KIPO 2016

S-2-hydroxy-3-methoxy-3, 3-dibenzylpropionic acid and preparation method thereof

The invention provides S-2-hydroxy-3-methoxy-3, 3-dibenzylpropionic acid and a preparation method thereof. The preparation method comprises 1, dissolving 2, 3-epoxy-3, 3-dibenzylpropionate in methanol, carrying out acid-catalyzed ring-opening, alkali metal hydroxide hydrolysis and reaction solution condensation, adding water into the condensed solution, filtering the solution after solids are separated, and carrying out solvent washing and purification to obtain refined 2-hydroxy-3-methoxy-3, 3-dibenzylpropionate, and 2, carrying out a reaction process on the refined 2-hydroxy-3-methoxy-3, 3-dibenzylpropionate and methyl L-prolinate, carrying out splitting to obtain methyl S-2-hydroxy-3-methoxy-3, 3-dibenzylpropionic acid-L-prolinate, adding an acid into the methyl S-2-hydroxy-3-methoxy-3, 3-dibenzylpropionic acid-L-prolinate so that the methyl S-2-hydroxy-3-methoxy-3, 3-dibenzylpropionic acid-L-prolinate is free and carrying out extraction, drying, condensation and recrystallization to obtain S-2-hydroxy-3-methoxy-3, 3-dibenzylpropionic acid. The preparation method has simple processes, can produce high purity S-2-hydroxy-3-methoxy-3, 3-dibenzylpropionic acid, can guarantee ambrisentan reaching the standard, can shorten a synthesis period, is free of an acid binding agent in a splitting stage and reduces a cost.

New carboxylic acid derivative, its production and its use

Heterocyclyl-substd. propanoic acids and their derivs., of formula (I), are new. R = formyl, tetrazolyl, nitrile, COOH or a gp. that can be hydrolysed to COOH; X = N or CR14; R2 = H, OH, NH2, alkylamino, dialkylamino, halo, alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio; R14 = H or 1-5 C alkyl; R3 = R2 or alkoxyimino; or CR3 + CR14 = 5 or 6 membered alkylene or alkenyl ring (opt. substd. by 1-2 alkyl) in which a methylene can be replaced by O, S, NH or alkylamino; R4, R5 = phenyl or naphthyl (both opt. substd. by one or more halo, NO2, CN, OH, alkyl, haloalkyl, alkoxy, haloalkyloxy, phenoxy, alkylthio, NH2, alkylamine or dialkylamino) or 3-7 C cycloalkyl; or the phenyl or naphthyl gps. are opt. bonded at the O- position (by a bond, CH2, O, S, SO2, ethylene, ethenylene or opt. alkylated amino); R6 = H, 1-8 C alkyl, 2-6 C alkenyl, 3-6 C alkynyl, 3-8 C cycloalkyl (all opt. substd. by 1 or more halo, NO2, CN, alkoxy 3-6 C alkenyloxy, 3-6 C alkynyloxy, alkylthio, haloalkoxy, alkylcarbonyl, alkoxycarbonyl, 3-8 C alkylcarbonylalkyl, alkylamino, dialkylamino, phenyl, Ph or OPh), Ar or Het; Y = S, O or bond; Q = S, O, SO, SO2 or bond; Ph = substd. phenyl, where substits. are halo, NO2, CN, alkyl, haloalkyl, alkoxy, haloalkoxy or alkylthio; Ar = phenyl or naphthyl (both opt. substd. by 1 or more halo, NO2, CN, OH, NH2, alkylamino, dialkylamino or OCH2CH2O); Het = 5 or 6 membered heteroaromatic with 1-3 N atoms and/or one S or O (opt. substd. by 1-4 halo and/or 1 or 2 alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, phenyl, phenoxy or phenyl carbonyl (where the phenyl is opt. substd. by 1-5 halo and/or 1-3 alkyl, haloalkyl, alkoxy, haloalkoxy and/or alkylthio)); alkyl and alkoxy have 1-4 C unless otherwise stated; provided that R6 is not H when Q = bond.

PREPARATION PROCESS OF CARBOXYLIC ACID DERIVATIVES AND INTERMEDIATES THEREOF

A cocrystal of (S)-2-hydroxy-3-methoxy-3,3-diphenylpropanoic acid and an amino acid, in particular L-valine or L-2-aminobutyric acid, their preparation processes, as well as the preparation process of Ambrisentan or Darusentan using any of the cocrystals of the invention.