219861-08-2

Basic information

• Product Name: Escitalopram oxalate
• Synonyms: (S)-CITALOPRAM;1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofuran-carbonitrile oxalate;ESCITALOPRAM OXALATE;S-(+)-CITAPROLAM OXALATE;S-(+)-1-3-(dimethyl-amino)propyl-1-(p-fluorophenyl)-5-phthalancarbonitrileoxalate;ESCIFALOPRAMOXALATE;(1S)-1-[3-(Dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-5-isobenzofurancarbonitrile Ethanedioate;Cipralex
• CAS NO: 219861-08-2
• Molecular Formula: C₂H₂O₄*C₂₀H₂₁FN₂O
• Molecular Weight: 414.43
• EINECS: 1806241-263-5
• Product Categories: Antidepressant;Heterocyclic Compounds;Intermediates & Fine Chemicals;Neurochemicals;Pharmaceuticals;Isotope Labeled Compounds;Escitalopram;Isotope Labelled Compounds;Aromatics;Chiral Reagents;Heterocycles;Pharmaceutical intermdiate;CHLORESIUM;Other APIs;Inhibitors
• Mol File: 219861-08-2.mol
• Article Data: 29

Chemical Properties

• Melting Point: 152-153°C
• Boiling Point: 428.3 °C at 760 mmHg
• Flash Point: 212.8 °C
• Appearance: white to tan/
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: DMSO: ≥15mg/mL
• Stability: Hygroscopic
• Merck: 14,2318
• CAS DataBase Reference: Escitalopram oxalate(CAS DataBase Reference)
• NIST Chemistry Reference: Escitalopram oxalate(219861-08-2)
• EPA Substance Registry System: Escitalopram oxalate(219861-08-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: NP6333500
• Hazardous Substances Data: 219861-08-2(Hazardous Substances Data)

Usage

Description

Escitalopram was launched as Cipralex? in Switzerland, Sweden and UK for the treatment of depression and panic disorder. It is the S-enantiomer version of the selective serotonin reuptake inhibitor (SSRI) citalopram approved in 1989. It can be obtained from 5cyanophthalide by successive reactions with 4-fluorophenyl magnesium bromide and 3-(dimethylamino)propyl magnesium chloride. The resulting racemic diol can be resolved by several routes such as crystallization with a chiral acid. Finally, a two step cyclisation procedure affords escitalopram. Escitalopram is twice as effective as the racemate and over 100 fold more potent than the R-enantiomer in inhibiting the 5HT reuptake in vivo in rat brain synaptosomes. Moreover, it exhibits higher selectivity for the human serotonin transporter relative to the noradrenaline or dopamine transporters than any other currently available SSRl’s. In the mouse forced swim test, the duration of immobility (which reflects antidepressant activity) for escitalopram was comparable to citalopram and greater than (R)-citalopram. Clinical trials in patients with panic disorders or depression have shown that escitalopram has a clinically relevant and significant effect. Additionally, it has a faster onset of antidepressant action than citalopram. Escitalopram has linear pharmacokinetics, with a long half-life (27-32 h). It is extensively metabolized in the liver via cytochromes P450 to S(+)-desmethyl and S(+)-didesmethyl citalopram. However, it has been shown to be a weak or negligible inhibitor of CYP450 drugmetabolizing enzymes in vitro. Escitalopram is well tolerated with nausea being the most common side effect.

Chemical Properties

White Solid

Originator

Lundbeck (Denmark)

Uses

Different sources of media describe the Uses of 219861-08-2 differently. You can refer to the following data:
1. Escitalopram oxalate may be used as a pharmaceutical primary standard for the quantification of the analyte in pharmaceutical formulations using analytical techniques.
2. An inhibitor of serotonin (5-HT) uptake. Antidepressant
3. A labelled inhibitor of serotonin (5-HT) uptake. Antidepressant
4. antineoplastic

Brand name

Lexapro (Forest).

General Description

Pharmaceutical secondary standards for application in quality control, provide pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards. Escitalopram Oxalate, a highly selective serotonin re-uptake inhibitor antidepressant, is a pure S-enantiomer of the racemic, bicyclic pthalates derivatives of citalopram. It is mainly developed for the treatment of depression and anxiety disorders.

Biochem/physiol Actions

Escitalopram is a selective serotonin reuptake inhibitor (SSRI), the S-enantiomer and eutomer of citalopram.

Synthesis

The synthesis of escitalopram was carried out in several different routes [30-33]. 5-Cyanophthalide (72) was treated with Grignard reagent 73 at 0°C to provide intermediate 75 which was reacted in situ with another Grignard reagent 76 to afford the diol in a one-pot process. Racemic diol 77 was resolved using (+)-p-toluoyltartaric acid to afford desired S isomer 78 in 55% yield. The ring closure reaction was carried out at 0°C using methanesulfonyl chloride in toluene to furnish escitalopram (7) in 60% yield.

InChI:InChI=1/C20H21FN2O.C2H2O4/c1-23(2)11-3-10-20(17-5-7-18(21)8-6-17)19-9-4-15(13-22)12-16(19)14-24-20;3-1(4)2(5)6/h4-9,12H,3,10-11,14H2,1-2H3;(H,3,4)(H,5,6)/t20-;/m1./s1

Synthetic route

oxalic acid (144-62-7) + (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile (488787-59-3) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Stage #1: (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile With methanesulfonyl chloride; triethylamine In dichloromethane at 5℃; for 2h; Stage #2: oxalic acid	65%
Stage #1: (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile With potassium carbonate; 2,5-dichloronitrobenzene In dimethyl sulfoxide at 20 - 100℃; for 15h; Stage #2: oxalic acid In acetone at 30℃;
Stage #1: (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile With bis(phenyl) carbonate; sodium methylate In acetonitrile at 79 - 80℃; for 4h; Stage #2: oxalic acid In ethyl acetate for 3h; Reagent/catalyst; Reflux;	3.02 g

(1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile hemi-(+)-di-(p-toluoyl) tartaric acid salt + oxalic acid (144-62-7) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Stage #1: (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile hemi-(+)-di-(p-toluoyl) tartaric acid salt With sodium hydroxide In diethyl ether; water at 25℃; for 0.5h; Stage #2: With triethylamine In diethyl ether; water; toluene at 5℃; for 0.5h; Stage #3: oxalic acid Further stages;	85%
Stage #1: (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile hemi-(+)-di-(p-toluoyl) tartaric acid salt With ammonia In dichloromethane; water pH=9; Stage #2: With triethylamine; p-toluenesulfonyl chloride In dichloromethane at 5℃; for 1h; Stage #3: oxalic acid In acetone	n/a

(S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(4-nitrobenzoyloxymethyl)benzonitrile hydrochloride + oxalic acid (144-62-7) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Stage #1: (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(4-nitrobenzoyloxymethyl)benzonitrile hydrochloride With sodium hydrogencarbonate In water; ethyl acetate Stage #2: With potassium carbonate In dimethyl sulfoxide at 90 - 100℃; for 2h; Stage #3: oxalic acid	82%

oxalic acid (144-62-7) + escitalopram (128196-01-0) → escitalopram oxalate (219861-08-2)

Conditions	Yield
In acetone at 25 - 30℃; Industry scale;	98.57%
In acetonitrile at 50℃; for 0.5h;	89%
In acetone at 25 - 45℃; for 1.5h;	85%

(S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(2-nitro-4-chlorophenoxymethyl)benzonitrile hydrochloride (878007-22-8) + oxalic acid (144-62-7) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Stage #1: (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(2-nitro-4-chlorophenoxymethyl)benzonitrile hydrochloride With potassium carbonate at 100℃; for 0.5h; Stage #2: oxalic acid	64%

formaldehyd (50-00-0) + oxalic acid (144-62-7) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Stage #1: 1-(3-aminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile; (-)-di-p-toluoyl tartaric acid salt With sodium hydroxide In water; toluene pH=11 - 13; Stage #2: formaldehyd; formic acid In water at 95 - 100℃; for 3 - 4h; Stage #3: oxalic acid With hydrogenchloride more than 3 stages;

(S)-citalopram (L)-tartrate (1073819-95-0) + oxalic acid (144-62-7) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Stage #1: (S)-citalopram (L)-tartrate With sodium hydroxide In water; ethyl acetate pH=10; Stage #2: oxalic acid In ethyl acetate

escitalopram (128196-01-0) → escitalopram oxalate (219861-08-2)

Conditions	Yield
With oxalic acid In acetone at 10℃; for 1h;
With oxalic acid In ethanol at 5 - 20℃; for 10.5h; Product distribution / selectivity;

oxalic acid (144-62-7) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Stage #1: escitalopram With hydrogen bromide In isopropyl alcohol at 20℃; for 2.16667h; pH=3.5 - 4; Stage #2: With ammonia In water; ethyl acetate for 0.5h; pH=9 - 9.5; Stage #3: oxalic acid In isopropyl alcohol at 20 - 40℃; for 2.16667h; Purification / work up;
Stage #1: oxalic acid With ammonia In water; ethyl acetate pH=9 - 9.5; Stage #2: oxalic acid In isopropyl alcohol at 20 - 40℃; for 2.16667h; Purification / work up;
Stage #1: (+)-(S)-citalopram hydrobromide With ammonia In water; ethyl acetate pH=9 - 9.5; Stage #2: oxalic acid In isopropyl alcohol at 20 - 40℃; for 2.16667h; Purification / work up;

4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile (103146-25-4) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: isopropyl alcohol / 3 h / 20 - 45 °C 2.1: ammonia / water / pH ~ 9 2.2: 3 h / -5 °C 3.1: isopropyl alcohol / 0.5 h / 50 - 60 °C View Scheme
Multi-step reaction with 3 steps 1.1: isopropyl alcohol / 25 - 70 °C / Resolution of racemate 2.1: ammonium hydroxide / dichloromethane; water / 1 h / 5 - 15 °C 2.2: -5 - 5 °C 3.1: acetone / 20 - 40 °C View Scheme
Multi-step reaction with 4 steps 1.1: isopropyl alcohol / 25 - 35 °C 2.1: sodium hydroxide / diethyl ether; water / 0.5 h / 25 °C 3.1: triethylamine / toluene / 0.5 h / 5 °C 3.2: 1 h / 5 °C 4.1: acetone / 1.5 h / 25 - 45 °C View Scheme

Citalopram oxalate → (-)-Citalopram oxalate + escitalopram oxalate (219861-08-2)

Conditions	Yield
With stainless steel column (100 mm L x 4.6 mm i.d) packed with iniferter-mediated grafting of molecularly imprinted polymers on porous silica beads In acetonitrile at 40℃; pH=3; Resolution of racemate;

4-flourophenylmagnesium bromide (352-13-6) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: tetrahydrofuran / 0.25 h / -5 °C 1.2: 0.5 h / -5 - 20 °C 1.3: pH 2 2.1: isopropyl alcohol / 3 h / 20 - 45 °C 3.1: ammonia / water / pH ~ 9 3.2: 3 h / -5 °C 4.1: isopropyl alcohol / 0.5 h / 50 - 60 °C View Scheme
Multi-step reaction with 5 steps 1.1: tetrahydrofuran / 4 h / 5 - 15 °C / Inert atmosphere 1.2: 4 h / 0 - 15 °C 2.1: hydrogen bromide / 1.5 h / 5 - 30 °C 3.1: sodium hydroxide / water / 0.5 h / 25 °C 3.2: 4 h / 25 - 40 °C 4.1: sodium hydroxide / water; toluene / 0.5 h / 25 °C 4.2: 0.25 h / 25 °C 4.3: 1 h / -15 °C 5.1: acetonitrile / 4.5 h / 25 - 50 °C View Scheme

3-(N,N-dimethylamino)propylmagnesium chloride (19070-16-7) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: tetrahydrofuran / 0.25 h / -5 °C 1.2: 0.5 h / -5 - 20 °C 1.3: pH 2 2.1: isopropyl alcohol / 3 h / 20 - 45 °C 3.1: ammonia / water / pH ~ 9 3.2: 3 h / -5 °C 4.1: isopropyl alcohol / 0.5 h / 50 - 60 °C View Scheme
Multi-step reaction with 5 steps 1.1: tetrahydrofuran / 4 h / 5 - 15 °C / Inert atmosphere 1.2: 4 h / 0 - 15 °C 2.1: hydrogen bromide / 1.5 h / 5 - 30 °C 3.1: sodium hydroxide / water / 0.5 h / 25 °C 3.2: 4 h / 25 - 40 °C 4.1: sodium hydroxide / water; toluene / 0.5 h / 25 °C 4.2: 0.25 h / 25 °C 4.3: 1 h / -15 °C 5.1: acetonitrile / 4.5 h / 25 - 50 °C View Scheme

1-Bromo-4-fluorobenzene (460-00-4) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: iodine; magnesium / tetrahydrofuran / 5 h / 80 - 85 °C / Reflux 2.1: tetrahydrofuran / 0.25 h / -5 °C 2.2: 0.5 h / -5 - 20 °C 2.3: pH 2 3.1: isopropyl alcohol / 3 h / 20 - 45 °C 4.1: ammonia / water / pH ~ 9 4.2: 3 h / -5 °C 5.1: isopropyl alcohol / 0.5 h / 50 - 60 °C View Scheme

3-(dimethylamino)propyl chloride hydrochloride (5407-04-5) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: potassium hydroxide / water / 0 - 5 °C 1.2: 4 h / 100 - 110 °C / Reflux 2.1: tetrahydrofuran / 0.25 h / -5 °C 2.2: 0.5 h / -5 - 20 °C 2.3: pH 2 3.1: isopropyl alcohol / 3 h / 20 - 45 °C 4.1: ammonia / water / pH ~ 9 4.2: 3 h / -5 °C 5.1: isopropyl alcohol / 0.5 h / 50 - 60 °C View Scheme

(R)-4-(4-dimethylamino-1-(4'-fluorophenyl)-1-hydroxybutyl)-3-hydroxymethylbenzonitrile, salt with (+)-O,O'-di-p-toluoyltartaric acid (917483-01-3) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ammonia / water / pH ~ 9 1.2: 3 h / -5 °C 2.1: isopropyl alcohol / 0.5 h / 50 - 60 °C View Scheme

(-)-(S)-4-(4-dimethylamino-1-(4'-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)-benzonitrile (+)-di-p-toluoyl-D-tartaric acid salt → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: ammonium hydroxide / dichloromethane; water / 1 h / 5 - 15 °C 1.2: -5 - 5 °C 2.1: acetone / 20 - 40 °C View Scheme

1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile (82104-74-3) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: tetrahydrofuran / 4 h / 5 - 15 °C / Inert atmosphere 1.2: 4 h / 0 - 15 °C 2.1: hydrogen bromide / 1.5 h / 5 - 30 °C 3.1: sodium hydroxide / water / 0.5 h / 25 °C 3.2: 4 h / 25 - 40 °C 4.1: sodium hydroxide / water; toluene / 0.5 h / 25 °C 4.2: 0.25 h / 25 °C 4.3: 1 h / -15 °C 5.1: acetonitrile / 4.5 h / 25 - 50 °C View Scheme

4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile hydrobromide (103146-26-5) → escitalopram oxalate (219861-08-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water / 0.5 h / 25 °C 1.2: 4 h / 25 - 40 °C 2.1: sodium hydroxide / water; toluene / 0.5 h / 25 °C 2.2: 0.25 h / 25 °C 2.3: 1 h / -15 °C 3.1: acetonitrile / 4.5 h / 25 - 50 °C View Scheme

Upstream product

• 103146-26-5 4-(4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)benzonitrile hydrobromide 
• 82104-74-3 1-oxo-1,3-dihydro-isobenzofuran-5-carbonitrile 
• 144-62-7 oxalic acid 
• 878007-22-8 (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(2-nitro-4-chlorophenoxymethyl)benzonitrile hydrochloride 
• 128173-53-5 (-)-(S)-4-(4-dimethylamino-1-(4'-fluorophenyl)-1-hydroxybutyl)-3-(hydroxymethyl)-benzonitrile (+)-di-p-toluoyl-D-tartaric acid salt 
• 917483-01-3 (R)-4-(4-dimethylamino-1-(4'-fluorophenyl)-1-hydroxybutyl)-3-hydroxymethylbenzonitrile, salt with (+)-O,O'-di-p-toluoyltartaric acid 
• 19070-16-7 3-(N,N-dimethylamino)propylmagnesium chloride 
• 5407-04-5 3-(dimethylamino)propyl chloride hydrochloride 
• 352-13-6 4-flourophenylmagnesium bromide 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 103146-25-4 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile 
• 128173-53-5 (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)benzonitrile hemi-(+)-di-(p-toluoyl) tartaric acid salt 
• 488787-59-3 (S)-(-)-4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxy-1-butyl]-3-(hydroxymethyl)benzonitrile 
• 1073819-95-0 (S)-citalopram (L)-tartrate 

Relevant articles and documents

Iniferter-mediated grafting of molecularly imprinted polymers on porous silica beads for the enantiomeric resolution of drugs

A surface-imprinted chiral stationary phase for the enantiomeric resolution of the antidepressant drug, citalopram, is presented in this work. N, N′-diethylaminodithiocarbamoylpropyl(trimethoxy)silane has been used as silane iniferter for the surface functionalization of the solid silica support. A molecularly imprinted polymer thin film, in the nm scale, was then grafted on the silanized silica using itaconic acid as the functional monomer and ethylene glycol dimethacrylate as the cross-linker in the presence of the template S-citalopram. The total monomer amount was calculated to obtain the desired thickness. Non-imprinted stationary phases were prepared similarly in the absence of S-citalopram. Characterization of the materials was carried out by scanning electron microscopy, thermogravimetric analysis, elemental analysis and Fourier transform infrared spectroscopy. Stationary phases have been applied to the chromatographic separation of the target. Conditions for best chromatographic resolution of the enantiomers were optimized, and it was found that a mobile phase consisting of a mixture of formate buffer (40 mM, pH 3) and acetonitrile (30:70 v/v) at 40 °C provided best results. Binding behaviour of the developed material was finally assessed by batch rebinding experiments. The obtained binding isotherm was fitted to different binding models being the Freundlich-Langmuir model, the one that best fitted the experimental data. The developed material has shown high selectivity for the target enantiomer, and the stationary phase could be undoubtedly exploited for chiral separation of the drug.

PROCESS FOR PRODUCING HYDROBROMIDE OF DIOL COMPOUND

PROBLEM TO BE SOLVED: To provide a method for producing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hydrobromide with a high purity and a high isolation yield. SOLUTION: Provided is a process for producing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hydrobromide characterized in bringing 4-[4-(dimethylamino)-1-(4-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile and hydrogen bromide into contact in a mixed solvent of an ester-based solvent and water. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

PRODUCTION METHOD OF (1S)-4-[4-(DIMETHYLAMINO)-1-(4'-FLUOROPHENYL)-1-HYDROXYBUTYL]-3-(HYDROXYMETHYL)-BENZONITRILE HEMI(+)-DI-(p-TOLUOYL) TARTRATE, AND PRODUCTION METHOD OF (1S)-1-[3-(DIMETHYLAMINO)PROPYL]-1-(4-FLUOROPHENYL)-1,3-DIHYDROISOBENZOFURAN-5-CARBONITRILE AND SALT THEREOF USING THE TARTRATE

PROBLEM TO BE SOLVED: To provide a (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate having extremely high optical purity, and escitalopram having extremely high optical purity and its salt obtained from the above tartrate. SOLUTION: A production method is used, in which a crude (1S)-4-[4-(dimethylamino)-1-(4'-fluorophenyl)-1-hydroxybutyl]-3-(hydroxymethyl)-benzonitrile hemi(+)-di-(p-toluoyl) tartrate is recrystallized in a mixture solvent of alcohol and water, with the content of the water being 3.0 to 15.0 mass% in the mixture solvent of the alcohol and water, so as to obtain a recrystallized material of the above tartrate having extremely high optical purity. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT