32345-59-8

Basic information

• Product Name: 2-CHLORO-MANDELIC ACID METHYL ESTER
• Synonyms: 2-CHLORO-MANDELIC ACID METHYL ESTER;(R)-Methyl 2-hydroxy-2-(2-chlorophenyl)acetate;Methyl (R)-o-chloromandelate;Methyl 2-(2-chlorophenyl)-(R)-2-hydroxyacetate;Methyl 2-Chloro-D-mandelate;Methyl 2-Chloro-D-mandelate;(R)-Methyl 2-(2-chlorophenyl)-2-hydroxyacetate;methyl (R)-2-hydroxy-2-(2-chlorophenyl)acetate
• CAS NO: 32345-59-8
• Molecular Formula: C₉H₉ClO₃
• Molecular Weight: 200.61896
• EINECS: 1592732-453-0
• Mol File: 32345-59-8.mol

Chemical Properties

• Melting Point: 34 °C
• Boiling Point: 297.663°C at 760 mmHg
• Flash Point: 133.822°C
• Appearance: /
• Density: 1.316g/cm³
• Vapor Pressure: 0.001mmHg at 25°C
• Refractive Index: 1.551
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: Chloroform, Dichloromethane, Methanol
• PKA: 11.82±0.20(Predicted)
• CAS DataBase Reference: 2-CHLORO-MANDELIC ACID METHYL ESTER(CAS DataBase Reference)
• NIST Chemistry Reference: 2-CHLORO-MANDELIC ACID METHYL ESTER(32345-59-8)
• EPA Substance Registry System: 2-CHLORO-MANDELIC ACID METHYL ESTER(32345-59-8)

Safety Data

• Hazardous Substances Data: 32345-59-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
2-CHLORO-MANDELIC ACID METHYL ESTER is used as an intermediate in the synthesis of Clopidogrel Carboxylic Acid [Methyl (R)-o-chloromandelate] Ester (C587320), which is an impurity of Clopidogrel (C587250). Clopidogrel is an antithrombotic agent, a medication that helps prevent blood clots from forming. The synthesis of this intermediate is crucial for the production of Clopidogrel, ensuring the availability of this important medication for treating conditions such as stroke, heart attack, and peripheral arterial disease.

InChI:InChI=1/C9H9ClO3/c1-13-9(12)8(11)6-4-2-3-5-7(6)10/h2-5,8,11H,1H3/t8-/m1/s1

Upstream product

• 67-56-1 methanol 
• 10421-85-9 (R)-2-chloromandelic acid 
• 34966-49-9 methyl 2-chlorobenzoylformate 
• 264882-00-0 methyl 2-(2-chlorophenyl)-2-diazoacetate 
• 156276-21-0 rac-methyl 2-chloromandelate 
• 2743-38-6 O,O'-dibenzoyl-L-tartaric acid 
• 108-05-4 vinyl acetate 
• 89-98-5 2-chloro-benzaldehyde 
• 10421-85-9 2-chloromandelic acid 
• 13312-84-0 2-chloromandelonitrile 

Downstream Products

• 1360591-38-3 (S)-(2-chlorophenyl)(2-hydroxy-6,7-dihydro-4H-thiophene[3,2-c]pyridin-5-yl)acetic acid methyl ester 
• 113665-84-2 (S)-(+)-clopidogrel 
• 120202-66-6 (S)-(+)-clopidogrel bisulfate 
• 223123-46-4 methyl (R)-2-(2-chlorophenyl)-2-benzenesulfonyloxyacetate 
• 1444502-89-9 2-(2-chlorophenyl)-N-methoxy-(R)-2-(t-butyl dimethylsiloxy)-N-methylacetamide 
• 1444502-99-1 1-(2-chlorophenyl)-(R)-1-(t-butyldimethyl-siloxy)-(S)-2-propanol 
• 1444502-94-6 1-(2-chlorophenyl)-(R)-1-(t-butyldimethyl-siloxy)propane-2-on 
• 1314097-38-5 (S)-methyl 2-(2-pivaloyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)acetate hydrochloride 

Relevant articles and documents

Calcium(II)-mediated resolution of methyl o-chloromandelate with chiral O,O′-dibenzoyltartaric acid in preparative scale

We report here the coordination-mediated resolution of methyl o-chloromandelate, which is a key intermediate for clopidogrel, in preparative scale. The reaction of CaO, optically pure (2R, 3R)-O,O′-dibenzoyltartaric acid, and methyl o-chloromandelate in ethanol solution afforded a mixed-ligands calcium(II) complex that was further purified by stirring of the crystals in hot methanol. Methyl (R)-o-chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (71%) by treatment of the complex with acid. At the same time, (2R, 3R)-O,O′-dibenzoyltartaric acid was recovered in 72% yield. In addition, methyl (S)-o-chloromandelate was obtained in good enantiomeric excess value (>99.5%) and yield (73%) by recovery from the mother liquor and resolution with the same procedure for methyl (R)-o-chloromandelate, except that (2S, 3S)-O,O′-dibenzoyltartaric acid was used as the resolving reagent.

Improved o-chlorobenzoylformate bioreduction by stabilizing aldo-keto reductase YtbE with additives

Asymmetric reduction of methyl o-chlorobenzoylformate (CBFM) using aldo-keto reductase YtbE is a potentially cost-effective and green technology in manufacturing methyl (R)-o-chloromandelate which is a key intermediate for synthesizing (S)-clopidogrel (a

Thienopyridine derivative, preparation method and application thereof

The invention relates to a thienopyridine derivative, a preparation method and application thereof. The thienopyridine derivative has a structure shown in the formula (I), wherein the group R1, R2, R3, R4, X1, X2 or X3 and m, n and w are as defined in the

Application of the redox system of Nocardia corallina B-276 in the enantioselective biotransformation of ketones and alcohols

The aim of this research was to evaluate the redox system of Nocardia corallina B-276 in the biotransformation of 1-phenyl-1-propanone (1a), 2-hydroxy-1-phenylethanone (2a) and methyl (2-chlorophenyl)(oxo)acetate (3a) into 1-phenylpropan-1-ol (1b), 1-phenyl-1,2-ethanediol (2b) and methyl (2-chlorophenyl)(hydroxy)acetate (3b). The biomass of N. corallina was obtained in a liquid medium with an initial pH of 8.50, but the pH changed during the 96 h of the culture media, the final pH was between 4.74 and 7.62. The N. corallina biomass biocatalyzed the enantioselective reduction of 1a–3a to the corresponding alcohols. Whereas, during the process of oxidation of the rac-alcohols 1b–3b, 1b was oxidized in enantioselective way, the oxidation of 2b was not selective, but 3b was biotransformed mainly to (R)-3b. These results are indicative that N. corallina produced reductases and oxidases, whereby the biocatalytic activity was influenced by the final pH of the culture media, the reaction time and structure of the substrate.

A preparation method of clopidogrel hydrogen sulfate type II

The invention discloses a preparation method of clopidogrel hydrogen sulfate type II. The method comprises the following steps: (4) taking clopidogrel free alkali as a raw material, and reacting the clopidogrel free alkali with (1R)-(-)-10-camphorsulfonic acid in a reaction solvent to obtain clopidogrel camphorsulfonate, and hydrolyzing under an alkaline condition to obtain clopidogrel free alkali; and then preparing the clopidogrel hydrogen sulfate type II by taking the clopidogrel free alkali obtained in the step (4) as a raw material. The synthetic route is simple, the used solvent is cheap, the cost is saved, the generation of waste liquid is reduced, the recycling of the solvent is improved, and the prepared clopidogrel hydrogen sulfate type II has the characteristics of high purity,good quality, high yield, good stability, suitability for industrial mass production and the like.

A preparation method of clopidogrel hydrogen sulfate type II

The invention discloses a preparation method of clopidogrel hydrogen sulfate type II. According to the method, clopidogrel hydrogen sulfate type II is prepared by taking clopidogrel free alkali as a raw material, and a preparation method of clopidogrel free alkali comprises the following steps: (1) preparing a reaction mixed solution of R-chloromandelic acid methyl ester by the reaction of R-chloromandelic acid and methanol in an organic solvent and in the presence of a catalyst; (2) mixing the reaction mixed solution of R-chloromandelic acid methyl ester with an organic base and a catalyst, reacting in the presence of benzenesulfonyl chloride to obtain a reaction mixed solution of methyl 2-benzenesulfonyl-2-chlorophenylacetate; (3) mixing the reaction mixed solution of methyl 2-benzenesulfonyl-2-chlorophenylacetate obtained in the step (2) with 4,5,6,7-Tetrahydrothieno[3,2,c] pyridine hydrochloride and potassium carbonate for reaction to obtain the clopidogrel free alkali. According to the method, the solvent does not need to be supplemented in the last two steps, the solvent is directly used, and the reaction liquid concentration time is saved.

Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta-1 and beta-2 adrenergic receptors

A series of (-)-nornuciferidine derivatives was synthesized and the non-natural enantiomer of the aporphine alkaloid was discovered to be a potent β1- and β2-adrenergic receptor ligand that antagonized isoproterenol and procaterol induced cyclic AMP increases from adenylyl cyclase, respectively. Progressive deconstruction of the tetracyclic scaffold to less complex cyclic and acyclic analogues revealed that the conformationally restricted (6a-R,7-R)-7-hydroxyaporphine 2 (AK-2-202) was necessary for efficient receptor binding and antagonism.

Optically active 2-hydroxy tetrahydro Thienopyridine derivatives and process for their preparation and use

The invention provides an optically active 2-hydroxyltetrahydrothienopyridine derivative shown by formula I, or a pharmaceutically acceptable salt, solvate, polycrystal, enantiomer or racemization mixture thereof, wherein in the formula I, R1 is F, Cl, Br

Improved apparent enantioselectivity of a hydrolase by sequential hydrolysis and racemization

Further improvement of the enantioselectivity of hydrolases with moderate enantioselectivity is of important significance to fulfill the requirement in industrial application. Herein, a strategy based on sequential hydrolysis and racemization was adopted, using esterase BioH from Escherichia coli as an example. After coupling with a mandelate racemase, the E value of esterase BioH toward methyl (S)-o-chloromandelate was enhanced from 73 to 162, demonstrating the effectiveness of this strategy.

Altering the substrate specificity of reductase CgKR1 from Candida glabrata by protein engineering for bioreduction of aromatic α-keto esters

A versatile keto ester reductase CgKR1, exhibiting a broad substrate spectrum, was obtained from Candida glabrata by genome data mining. It showed the highest activity toward an aliphatic β-keto ester, ethyl 4-chloro-3-oxobutanoate (COBE), but much lower activity toward bulkier α-keto esters with an aromatic group, such as methyl ortho- chlorobenzoylformate (CBFM) and ethyl 2-oxo-4-phenylbutyrate (OPBE). By rational design of the active pocket, the substrate specificity of the reductase was significantly altered and this tailor-made reductase showed a much higher activity toward aromatic α-keto esters (～7-fold increase in k cat/Km toward CBFM) and lower activity toward aliphatic keto esters (～12-fold decrease in kcat/Km toward COBE). Meanwhile, the thermostability of the reductase was enhanced by a consensus approach. Such improvements may yield practical catalysts for the asymmetric bioreduction of these aromatic α-keto esters