32634-68-7

Basic information

• Product Name: 2,3-Di-O-para-toluoyl-D-tartaric acid
• Synonyms: RivastigMine USP RC A;RivastigMine Related CoMpound A;D- twoMethylbenzoyltartaric acid;D - 2 Methyl benzoyl tartaric acid;(+)-Di-1,4-toluoyl-D-tartaric acid [S(R*,R*)]-2,3-bis[(4-methylbenzoyl)oxy]succinic acid;(+)-2,3-Di-p-toluoyl-D-tartaric acid;(+)-Di-p-toluoyl-D-tartaric acid;(+)- Ditoluoyltartaric acid
• CAS NO: 32634-68-7
• Molecular Formula: C₂₀H₁₈O₈
• Molecular Weight: 386.35
• EINECS: 251-132-2
• Product Categories: Pharmaceutical Intermediates;FINE Chemical & INTERMEDIATES;Chiral Compounds;Miscellaneous;chiral;Carboxylic Acids (Chiral);Chiral Building Blocks;for Resolution of Bases;Optical Resolution;Synthetic Organic Chemistry;CHIRAL CHEMICALS;Hydroxy Acids & Deriv.;Chiral Compound;Inhibitors
• Mol File: 32634-68-7.mol
• Article Data: 4

Chemical Properties

• Melting Point: 169-171 °C(lit.)
• Boiling Point: 432.57°C (rough estimate)
• Flash Point: 223.2 °C
• Appearance: /
• Density: 1.3084 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 139 ° (C=1, EtOH)
• Storage Temp.: Refrigerator
• Solubility: DMSO (Slightly), Ethanol (Sparingly), Methanol (Slightly)
• PKA: 1.46±0.25(Predicted)
• Water Solubility: 112.55mg/L at 25℃
• BRN: 3225584
• CAS DataBase Reference: 2,3-Di-O-para-toluoyl-D-tartaric acid(CAS DataBase Reference)
• NIST Chemistry Reference: 2,3-Di-O-para-toluoyl-D-tartaric acid(32634-68-7)
• EPA Substance Registry System: 2,3-Di-O-para-toluoyl-D-tartaric acid(32634-68-7)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-36/37-26
• WGK Germany: 3
• F: 3-10
• TSCA: T
• Hazardous Substances Data: 32634-68-7(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powde

Uses

Different sources of media describe the Uses of 32634-68-7 differently. You can refer to the following data:
1. blood volume expander
2. Inhibitor of enzyme. Rivastigmine USP Related Compound A.

Flammability and Explosibility

Notclassified

InChI:InChI=1/C18H18O6/c1-11-3-7-13(8-4-11)23-15(17(19)20)16(18(21)22)24-14-9-5-12(2)6-10-14/h3-10,15-16H,1-2H3,(H,19,20)(H,21,22)

Synthetic route

rac-O,O'-di-p-toluoyltartaric acid (32634-66-5, 32634-68-7, 100168-11-4, 104528-81-6) → (2S,3S)-di-4-toluoyltartaric acid (32634-68-7)

Conditions	Yield
ueber das Cinchonin-Salz;

di-O-p-toluoyl-Dg-tartaric acid-anhydride → (2S,3S)-di-4-toluoyltartaric acid (32634-68-7)

Conditions	Yield
With water; acetone

(R)-2-cyclopropylaminocyclohexanol di-p-toluoyl-D-tartrate (339546-21-3) → (R)-2-cyclopropylaminocyclohexanol (339546-20-2) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7)

Conditions	Yield
With sodium hydroxide In water at 20 - 30℃; for 1h; Product distribution / selectivity;	A n/a B n/a

(+)-di-O,O'-toluoyl-D-tartaric acid mono-NH4 salt → (2S,3S)-di-4-toluoyltartaric acid (32634-68-7)

Conditions	Yield
With Amberlite 1R In isopropyl alcohol Product distribution / selectivity;
With hydrogenchloride In dichloromethane; water pH=< 0.5; Product distribution / selectivity;

(3S,4S)-2,5-dioxotetrahydrofuran-3,4-diyl bis(4-methylbenzoate) (72842-25-2) → (2S,3S)-di-4-toluoyltartaric acid (32634-68-7)

Conditions	Yield
With water In toluene for 5h; Reflux; Large scale;	374.4g

rac-O,O'-di-p-toluoyltartaric acid (32634-66-5, 32634-68-7, 100168-11-4, 104528-81-6) → Di-p-toluoyl-L-tartaric acid (32634-66-5) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7)

Conditions	Yield
With C22H24N2(2+)*2CF3O3S(1-) In aq. acetate buffer at 20℃; pH=8.1; Resolution of racemate;

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + (R,S)-3-iso-butyl-4-aminobutyric acid (128013-69-4, 130912-52-6, 148553-50-8, 148553-51-9) → (S)-pregabalin O,O'-di-p-toluoyl-(D)-tartrate + (R)-pregabalin O,O'-di-p-toluoyl-(D)-tartrate

Conditions	Yield
In water; butan-1-ol at 20 - 25℃; Resolution of racemate;	A 98% B n/a

(R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine (753015-44-0) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (R)-5-((E)-2-pyrrolidin-3-ylvinyl)pyrimidine mono-di-p-toluoyl-D-tartarate (1228391-41-0)

Conditions	Yield
In ethanol Reflux;	96.1%
In ethanol Reflux;	96.1%

rac-trans-2-methylamino-cyclohexanol (20431-81-6) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → 2C7H15NO*C20H18O8 + trans-2-(methylamino)cyclohexanol (21651-84-3)

Conditions	Yield
In ethanol at 45 - 60℃; for 1h;	A 95% B n/a

7-trifluoromethyl-2,3,4,5-tetrahydro-1,5-methylene-1H-3-benzazepine + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (1S,8R)-(+)-4-trifluoromethyl-10-azatricyclo[6.3.1.0(2,7)]dodeca-2(7),3,5-triene di-p-toluoyl-D-(-)-tartaric acid salt (873788-21-7)

Conditions	Yield
In acetonitrile at 82℃; for 1 - 24h; Product distribution / selectivity;	94%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + (4aS,8aS)-rel-3-methoxy-11-methyl-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro[4,3-cd]azepin-6-one (510-77-0, 1668-86-6, 7318-55-0) → [(-)-narwedine][di-p-toluoyl-D-tartrate]

Conditions	Yield
In ethanol at 40℃; Heating / reflux;	90%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + 2-(tert-butylamino)-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanol (54208-72-9) → 2C16H25NO3*C20H18O8

Conditions	Yield
In methanol for 0.166667h; Heating / reflux;	90%
In methanol for 0.25h; Heating / reflux;	73%

2-(1-aminoethyl)-N-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide (1095823-56-5) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → C12H10ClF3N4OS (1095825-44-7) + C12H10ClF3N4OS*C20H18O8 (1095823-60-1)

Conditions	Yield
In water; isopropyl alcohol at 45 - 53℃; for 21h; Purification / work up; Resolution of racemate;	A n/a B 88%

(8-hydroxy-4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-yl)acetonitrile + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → 2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethylaminedi-p-toluoyl-L-(-)-tartrate

Conditions	Yield
Stage #1: (8-hydroxy-4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-yl)acetonitrile With ammonia; hydrogen In ethanol at 55℃; under 18751.9 Torr; for 15h; Stage #2: (2S,3S)-di-4-toluoyltartaric acid at 20℃; for 0.75h; Temperature; Pressure; Solvent;	87.8%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + lofexidine hydrochloride (21498-08-8) → (+/-)-lofexidine di-p-toluoyl-D-tartarate + (+/+)-lofexidine di-p-toluoyl-D-tartarate

Conditions	Yield
In ethanol	A 87% B n/a

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + (S)-1-(2-piperidino-phenyl)-3-methyl-1-butylamine (108157-52-4) → (S)-3-methyl-1-(2-piperidino-phenyl)-1-butylamine di-p-toluoyl-D-tartaric acid salt (1098066-89-7)

Conditions	Yield
With toluene-4-sulfonic acid In methanol; water at 25 - 60℃; Product distribution / selectivity;	85.7%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + (4aS,8aS)-rel-3-methoxy-11-methyl-4a,5,9,10,11,12-hexahydro-6H-benzo[2,3]benzofuro[4,3-cd]azepin-6-one (510-77-0, 1668-86-6, 7318-55-0) → [(-)-narwedine]2[di-p-toluoyl-D-tartrate]

Conditions	Yield
In ethanol at 20 - 40℃; for 19h; Heating / reflux;	83%
In ethanol at 40℃; Heating / reflux;	79%

5-azaspiro[2.4]heptane-6-carboxylic acid + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (S)-5-azaspiro[2.4]heptane-6-carboxylic acid D-di-p-methylbenzoyltartrate

Conditions	Yield
Stage #1: 5-azaspiro[2.4]heptane-6-carboxylic acid; (2S,3S)-di-4-toluoyltartaric acid With acetic acid at 60℃; for 0.333333h; Stage #2: With ethyl acetate at 50℃; for 1.5h; Enzymatic reaction; Stage #3: With salicylaldehyde at 50℃; for 18h;	83%

1-Benzyl-3-methyl-4-piperidon (34737-89-8) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (R)-1-benzyl-3-methylpiperidin-4-one (2S,3S)-2,3-bis((4-methylbenzoyl)oxy)succinic acid salt

Conditions	Yield
In acetonitrile at 40℃; for 12h; Large scale;	83%
In acetonitrile at 40℃; for 12h; Large scale;	83%
In acetonitrile at 40℃; for 12h; Large scale;	83%

(S)-methyl 2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetate + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + ethyl acetate (141-78-6) → (S)-methyl 2-(8-fluoro-3-(2-methoxy-5-(trifluoromethyl)phenyl)-2-(4-(3-methoxyphenyl)piperazin-1-yl)-3,4-dihydroquinazolin-4-yl)acetate (2S,3S)-2,3-bis((4-methylbenzoyl)oxy)succinate ethyl acetate

Conditions	Yield
In toluene at 45℃; Inert atmosphere;	82%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (+)-(S,S)-D-O,O'-di-p-toluoyltartaric acid monosodium salt

Conditions	Yield
With sodium hydroxide In water for 0.166667h; Sonication;	82%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + [2R-[2α(R*),3α]]-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-(4-fluorophenyl)morpholine (171338-27-5) → BFM2-(D)-DTTA (1404074-27-6)

Conditions	Yield
In isopropyl alcohol at 50 - 55℃; for 0.333333h; Product distribution / selectivity; Industry scale;	80%

didesmethylcitalopram (62498-69-5) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → S-(+)-1-(3-amino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-5-carbonitrile (-)-di-p-toluoyltartrate + R-1-(3-amino-propyl)-1-(4-fluoro-phenyl)-1,3-dihydro-isobenzofuran-5-carbonitrile (-)-di-p-toluoyltartrate

Conditions	Yield
Stage #1: didesmethylcitalopram; (2S,3S)-di-4-toluoyltartaric acid In acetonitrile at 20℃; Stage #2: In water; acetonitrile at 0 - 60℃; Solvent;	A 80% B n/a

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + (R)-(+)-N,α-dimethylbenzylamine (5933-40-4) → (R)-N-methyl-α-methylbenzylammonium di-p-toluoyl-D-tartrate

Conditions	Yield
In methanol; ethyl acetate at 20℃; for 1h;	80%

N-methyl-N-[(S)-1-phenylethyl]amine (19131-99-8) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (S)-N-methyl-α-methylbenzylammonium di-p-toluoyl-D-tartrate

Conditions	Yield
In methanol; ethyl acetate at 20℃; for 1h;	80%

α-methyl-N-[3-[3-(trifluoromethyl)phenyl]propyl]-1-naphthalenemethanamine (1025064-33-8) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (R)-cinacalcet (-)-di-para-D-toluoyl tartrate

Conditions	Yield
In ethyl acetate at 25 - 65℃; for 0.75h;	78%

C30H30F4N4O4*C7H6O3 + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (2S,3S)-2,3-bis[(4-methylbenzoyl)oxy]succinic acid {(4S)-8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-(trifluormethyl)phenyl)-3,4-dihydroquinazolin-4-yl}acetic acid methyl ester (917389-30-1)

Conditions

Yield

Stage #1: C30H30F4N4O4*C7H6O3 With potassium phosphate In water; toluene at 20℃; for 1h; Stage #2: With potassium phosphate; (1S,2S,4S,5R)-1-(3,5-bis(trifluoromethyl)benzyl)-2-((R)-hydroxy(1-(3-(trifluoromethyl)benzyl)quinolin-1-ium-4-yl)methyl)-5-vinylquinuclidin-1-ium bromide In water; N,N-dimethyl-formamide; toluene at 0℃; Stage #3: (2S,3S)-di-4-toluoyltartaric acid In ethyl acetate; toluene at 20℃; for 12h;

78%

amfepramone (90-84-6, 39648-49-2, 39648-50-5) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → C20H18O8*C13H19NO

Conditions	Yield
With sodium hydroxide In water; acetone at 20℃;	78%

C15H18N2O2 + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → C20H18O8*C15H18N2O2

Conditions	Yield
In water; acetonitrile Solvent;	78%

trans-N-(2-hydroxycyclohexyl)-N-cyclopropylamine (726201-98-5) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (R)-2-cyclopropylaminocyclohexanol di-p-toluoyl-D-tartrate (339546-21-3)

Conditions	Yield
With hydrogenchloride In methanol; water at 20 - 70℃; for 2.5h; Resolution of racemate;	77.8%

rac-7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane (646055-67-6) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (S)-7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane mono-(+)-di-O,O'-p-toluoyl-D-tartrate (1174118-94-5)

Conditions	Yield
In ethanol at 20 - 50℃; Purification / work up; Reflux; Resolution of racemate;	76.4%

(±)-2-(pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-one (273748-55-3) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (2S)-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]octan-3-one di-p-toluoyl-D-tartrate (1111942-08-5)

Conditions	Yield
Stage #1: (±)-2-(pyridin-3-ylmethylidene)-1-azabicyclo[2.2.2]octan-3-one With hydrogen; palladium 10% on activated carbon In methanol at 20℃; for 12h; Industry scale; Stage #2: (2S,3S)-di-4-toluoyltartaric acid In ethanol at 15 - 30℃; for 13h; Industry scale; Heating / reflux;	76.2%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (3S,4S)-2,5-dioxotetrahydrofuran-3,4-diyl bis(4-methylbenzoate) (72842-25-2)

Conditions	Yield
With acetic anhydride at 85℃; for 2h;	76%

C23H24F3N (1206633-34-2) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → C20H18O8*(x)C23H24F3N

Conditions	Yield
In ethyl acetate at 25 - 65℃; for 0.75h;	74.3%

(2S,3S)-di-4-toluoyltartaric acid (32634-68-7) + 3-amino-5-phenyl-1,3-dihydro-2H-benzo[b]azepin-2-one → (S)-3-amino-5-phenyl-1,3-dihydro-2H-benzo[b]azepin-2-one

Conditions	Yield
Stage #1: (2S,3S)-di-4-toluoyltartaric acid; 3-amino-5-phenyl-1,3-dihydro-2H-benzo[b]azepin-2-one In 1,4-dioxane at 20℃; for 24h; Stage #2: With sodium hydroxide In water at 20℃; for 4h;	73.2%
Stage #1: (2S,3S)-di-4-toluoyltartaric acid; 3-amino-5-phenyl-1,3-dihydro-2H-benzo[b]azepin-2-one In 1,4-dioxane at 20℃; for 24h; Stage #2: With sodium hydroxide at 20℃; for 4h;	73.2%

(-)-(S)-N,N-dimethyl-1-phenylethylamine (17279-31-1) + (2S,3S)-di-4-toluoyltartaric acid (32634-68-7) → (S)-N,N-dimethyl-α-methylbenzylammonium di-p-toluoyl-D-tartrate

Conditions	Yield
In Isopropyl acetate Reflux;	73%

Upstream product

• 72842-25-2 (3S,4S)-2,5-dioxotetrahydrofuran-3,4-diyl bis(4-methylbenzoate) 
• 339546-21-3 (R)-2-cyclopropylaminocyclohexanol di-p-toluoyl-D-tartrate 
• 32634-66-5 rac-O,O'-di-p-toluoyltartaric acid 

Downstream Products

• 68935-25-1 l-nicotine di-(p-toluoyl)-d-tartrate 
• 644982-24-1 [1-(3,5-dichloro-phenyl)-ethyl]-methylamine di-p-toluoyl-D-tartrate salt 
• 928655-45-2 (+)-6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)-carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine di-p-toluyl-D-tartate 
• 144124-40-3 ethyl (3S,4R)-1,3-dimethyl-4-[3-(1-methylethoxy)phenyl]-4-piperidinyl ester carbonic acid (+)-D-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid 
• 1174118-94-5 (S)-7-(3-pyridinyl)-1,7-diazaspiro[4.4]nonane mono-(+)-di-O,O'-p-toluoyl-D-tartrate 

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