3972-36-9

Basic information

• Product Name: (S)-2-Benzylsuccinic acid
• Synonyms: (S)-2-BENZYLSUCCINIC ACID;(S)-2-BENZYL-1,4-BUTANEDIOIC ACID;Mitiglinide intermediate 2;Mitiglinide intermediate 8;(S)-2-Benzylsuccinic acid (Mitiglinide);(S)-2-Benzylsuccinic (2S)-2-benzylbutanedioic acid;Mitiglinide Impurity 1
• CAS NO: 3972-36-9
• Molecular Formula: C₁₁H₁₂O₄
• Molecular Weight: 208.21
• EINECS: 1806241-263-5
• Product Categories: Pharmaceutical material and intermeidates;Acids and Derivatives;APIs Intermediate
• Mol File: 3972-36-9.mol
• Article Data: 20

Chemical Properties

• Melting Point: 164.0 to 168.0 °C
• Boiling Point: 331.4 °C at 760 mmHg
• Flash Point: 168.4 °C
• Appearance: /
• Density: 1.29 g/cm³
• Vapor Pressure: 6.23E-05mmHg at 25°C
• Refractive Index: 1.567
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 3.97±0.10(Predicted)
• CAS DataBase Reference: (S)-2-Benzylsuccinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-2-Benzylsuccinic acid(3972-36-9)
• EPA Substance Registry System: (S)-2-Benzylsuccinic acid(3972-36-9)

Safety Data

• Hazardous Substances Data: 3972-36-9(Hazardous Substances Data)

Usage

General Description

(S)-2-Benzylsuccinic acid is a compound that belongs to the class of organic compounds known as phenylpropanoic acids. It is a solid, crystalline substance with a molecular formula of C14H14O4. (S)-2-Benzylsuccinic acid is primarily used in the production of pharmaceuticals and as an intermediate in the synthesis of other organic compounds. It has exhibited potential therapeutic properties and is being studied for its potential use in the treatment of various diseases and medical conditions. The compound's structure and properties make it a valuable ingredient in the synthesis of complex organic molecules, and it is an important building block in the field of medicinal chemistry.

InChI:InChI=1/C11H12O4/c12-10(13)7-9(11(14)15)6-8-4-2-1-3-5-8/h1-5,9H,6-7H2,(H,12,13)(H,14,15)/t9-/m0/s1

Synthetic route

(S)-3-benzyl-4-((R)-4-benzyl-2-oxooxazolidin-3-yl)-4-oxobutanoic acid (1141895-98-8) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With dihydrogen peroxide; lithium hydroxide In tetrahydrofuran; water at 0℃;	100%

bis[(S)-3-methyl-2-phenylbutylammonium] (S)-2-benzylsuccinate → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With sodium hydroxide In water	98.8%

phenylmethyl 3-carboxy-2(S)-(phenylmethyl)-1-propanoate (140903-48-6) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol for 2h; Ambient temperature;	97%

(Z)-2-benzylidenesuccinic acid (65756-81-2) → (2S)-benzylsuccinic acid (3972-36-9) + (R)-2-benzylsuccinic acid (21307-97-1)

Conditions	Yield
With hydrogen; triethylamine; Ru2Cl4((R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl)2 In tetrahydrofuran; toluene at 35℃; under 2206.5 Torr; for 24h; op = 90percent, var. cat. RuHCl*2<(+)-BINAP>; Title compound not separated from byproducts;	A 94% B n/a

(3S)-4-[(3aS,6R,7aS)-tetrahydro-8,8-dimethyl-2,2-dioxido-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-4-oxo-3-(phenylmethyl)butanoic acid (787635-23-8) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With lithium hydroxide; dihydrogen peroxide at 0 - 20℃; for 13h;	93%

2-benzylidenesuccinic acid (5653-88-3) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With Ru(OCOCH3)2{(S)-2,2'-bis(diphenylphosphino)-1,1'-dinaphthyl)}; hydrogen In methanol at 50℃; under 760.051 Torr; for 10h; Molecular sieve; Inert atmosphere; Large scale;	81%

(Z)-2-benzylidenesuccinic acid (65756-81-2) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With hydrogen; acetic acid; palladium on activated charcoal at 75℃; for 3h;	10%

2-benzylsuccinic acid (36092-42-9) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With (R)-1-phenyl-ethyl-amine

diethyl (S)-2-benzylsuccinate → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With sodium hydroxide In ethanol

trans-phenylitaconic acid (5653-88-3, 65756-81-2, 46427-07-0) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With formic acid; CF3SO3; triethylamine In dimethyl sulfoxide at 44.9℃; Rate constant;
With hydrogen; chloro(1,5-cyclooctadiene)rhodium(I) dimer; (2S,4S)-4-(Diphenylphosphino)-2-<(diphenylphosphino)-methyl>-N-phenoxycarbonylpyrrolidine In methanol; benzene at 20℃; under 760 Torr; for 4h;

trans-phenylitaconic acid (5653-88-3, 65756-81-2, 46427-07-0) → (2S)-benzylsuccinic acid (3972-36-9) + (R)-2-benzylsuccinic acid (21307-97-1)

Conditions	Yield
With hydrogen; triethylamine; complex of Rh(COD)*BF4 and (4R,5R)-(+)-MOD-DIOP In methanol at 30℃; under 760 Torr; for 40h;	A 79 % Spectr. B n/a
With hydrogen; triethylamine; <((R)-(1,1'-binaphthyl-2,2'-diyl)bis(diphenylphosphine))RuCl2>2NEt3 In tetrahydrofuran; ethanol at 35℃; under 1520 Torr; for 24h; RuHCl-bis<(R)-(+)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl>; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With <((R)-(1,1'-binaphthyl-2,2'-diyl)bis(diphenylphosphine))RuCl2>2NEt3; hydrogen; triethylamine In tetrahydrofuran; ethanol at 50℃; under 3800 Torr; for 24h; Title compound not separated from byproducts;
With hydrogen; triethylamine; hydridobis((R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl)ruthenium, PF6 salt In tetrahydrofuran; ethanol at 50℃; under 2280 Torr; for 24h; Yield given. Title compound not separated from byproducts;
With RuCl2(C6F5CN)2((S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl); hydrogen; triethylamine In tetrahydrofuran; ethanol at 50℃; under 3800 Torr; for 24h; Title compound not separated from byproducts;

diethyl (2S)-2-benzyl-3-cyanosuccinate → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With hydrogenchloride In acetic acid for 10h; Heating;

(S)-3-benzyl-4-methoxy-4-oxobutanoic acid (182247-45-6) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With sodium hydroxide In methanol

diazomethane (186581-53-3, 908094-01-9) + methanol (67-56-1) + (R)-3-Benzyl-pent-4-enenitrile (193147-43-2) → (2S)-benzylsuccinic acid (3972-36-9) + (R)-2-benzylsuccinic acid (21307-97-1)

(R)-2-benzyl-5-methyl-4-hexenoic acid → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With formic acid; dihydrogen peroxide; ozone 1.) MeOH; Yield given. Multistep reaction;

(S)-4-(tert-butoxy)-4-oxo-2-(1-phenylmethyl)butanoic acid (337518-87-3) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 0 - 20℃;	0.34 g

N,N'-fumaroyldi<(2R)-bornane-10,2-sultam> (123191-44-6) + benzylmagnesium chloride (6921-34-2) → (2S)-benzylsuccinic acid (3972-36-9) + (R)-2-benzylsuccinic acid (21307-97-1)

Conditions	Yield
Stage #1: N,N'-fumaroyldi<(2R)-bornane-10,2-sultam>; benzylmagnesium chloride In tetrahydrofuran; diethyl ether at -78℃; for 3h; Stage #2: With lithium hydroxide; dihydrogen peroxide In tetrahydrofuran; water at 0℃; for 7h; Title compound not separated from byproducts;

1-((3aS,6R,7aR)-8,8-dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)-3-phenylpropan-1-one (127392-81-8) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: NaHMDS / tetrahydrofuran / 0.5 h / -78 °C 1.2: 92 percent / tetrahydrofuran; hexamethylphosphoric acid triamide / 20 h / -78 - 25 °C 2.1: 84 percent / aq. LiOH; aq. H2O2 / tetrahydrofuran / 0 - 20 °C 3.1: 0.34 g / trifluoroacetic acid / CH2Cl2 / 0 - 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: NaHMDS / tetrahydrofuran / 0.5 h / -78 °C 1.2: 92 percent / tetrahydrofuran; hexamethylphosphoric acid triamide / 20 h / -78 - 25 °C 2.1: 87 percent / trifluoroacetic acid / CH2Cl2 / 0 - 20 °C 3.1: 93 percent / aq. H2O2; LiOH*H2O / 13 h / 0 - 20 °C View Scheme

hydrocinnamic acid chloride (645-45-4) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: NaH / toluene; tetrahydrofuran / 1 h / 20 °C 1.2: 91 percent / tetrahydrofuran; toluene / 16 h 2.1: NaHMDS / tetrahydrofuran / 0.5 h / -78 °C 2.2: 92 percent / tetrahydrofuran; hexamethylphosphoric acid triamide / 20 h / -78 - 25 °C 3.1: 84 percent / aq. LiOH; aq. H2O2 / tetrahydrofuran / 0 - 20 °C 4.1: 0.34 g / trifluoroacetic acid / CH2Cl2 / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: NaH / toluene; tetrahydrofuran / 1 h / 20 °C 1.2: 91 percent / tetrahydrofuran; toluene / 16 h 2.1: NaHMDS / tetrahydrofuran / 0.5 h / -78 °C 2.2: 92 percent / tetrahydrofuran; hexamethylphosphoric acid triamide / 20 h / -78 - 25 °C 3.1: 87 percent / trifluoroacetic acid / CH2Cl2 / 0 - 20 °C 4.1: 93 percent / aq. H2O2; LiOH*H2O / 13 h / 0 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: triethylamine; dmap / dichloromethane / 2 h / 0 °C 2: lithium diisopropyl amide / tetrahydrofuran / 1 h / -70 - 20 °C 3: trifluoroacetic acid / dichloromethane / 48 h 4: dihydrogen peroxide; lithium hydroxide / tetrahydrofuran; water / 0 °C View Scheme

1,1-dimethylethyl (3S)-4-[(3aS,6R,7aS)-8,8-dimethyl-2,2-dioxidotetrahydro-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-4-oxo-3-(phenylmethyl)butanoate (787635-22-7) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / aq. LiOH; aq. H2O2 / tetrahydrofuran / 0 - 20 °C 2: 0.34 g / trifluoroacetic acid / CH2Cl2 / 0 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: 87 percent / trifluoroacetic acid / CH2Cl2 / 0 - 20 °C 2: 93 percent / aq. H2O2; LiOH*H2O / 13 h / 0 - 20 °C View Scheme

Z-methyl 4-(phenyl)-3-methoxycarbonylbut-3-enoate (65756-82-3) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaOH / methanol / 12 h / Heating 2: 10 percent / H2; acetic acid / 10 percent Pd/C / 3 h / 75 °C View Scheme

benzaldehyde (100-52-7) + methylacetylene metal salt → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: t-BuOK / 2-methyl-propan-2-ol / Heating 2: NaOH / methanol / 12 h / Heating 3: 10 percent / H2; acetic acid / 10 percent Pd/C / 3 h / 75 °C View Scheme

Benzyl (2S)-2-Benzyl-3-t-butoxycarbonyl Propionate (131288-25-0) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 82 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 2: 97 percent / H2 / Pd/C / methanol / 2 h / Ambient temperature View Scheme

(5R)-(-)-(1'-oxo-3'-phenylpropyl)-5,3,3-trimethylpyrrolidin-2-one (155956-29-9) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: 79 percent / LDA / tetrahydrofuran / 1.) -78 deg C, 1 h, 2.) -78 deg C to r.t., overnight 2: 94 percent / BuLi / tetrahydrofuran / 1.) -78 deg C to 0 deg C, 10 min, 2.) 0 deg C, 1 h 3: 82 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 4: 97 percent / H2 / Pd/C / methanol / 2 h / Ambient temperature View Scheme

(S)-3-Benzyl-4-oxo-4-((R)-3,3,5-trimethyl-2-oxo-pyrrolidin-1-yl)-butyric acid tert-butyl ester (215373-19-6) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / BuLi / tetrahydrofuran / 1.) -78 deg C to 0 deg C, 10 min, 2.) 0 deg C, 1 h 2: 82 percent / TFA / CH2Cl2 / 1 h / Ambient temperature 3: 97 percent / H2 / Pd/C / methanol / 2 h / Ambient temperature View Scheme

dimethyl 2-benzylsuccinate (35262-43-2) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1) porcine pancrease lipase, 3) porcine pancrease lipase / 1) 0.1M KHPO4 buffer (pH = 7.2), 3) 0.1M KHPO4 buffer (pH = 7.2) 2: 1M NaOH / methanol View Scheme

ethyl (R)-2-hydroxy-3-phenylpropanoate (15399-05-0, 15399-27-6, 20918-87-0, 20918-88-1) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: 8.7 percent / diethyl azodicarboxylate, triphenylphosphine / tetrahydrofuran / 2 h / Ambient temperature 2: conc. aq. HCl / acetic acid / 10 h / Heating View Scheme

1,4-diethyl 2-benzylsuccinate (21654-18-2, 79909-18-5) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1: α-chymotrypsin, aq. NaOH 2: aq. NaOH / ethanol View Scheme

(R)-4-benzyl-3-(3-phenyl-propionyl)-oxazolidin-2-one (136159-65-4) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium diisopropyl amide / tetrahydrofuran / 1 h / -70 - 20 °C 2: trifluoroacetic acid / dichloromethane / 48 h 3: dihydrogen peroxide; lithium hydroxide / tetrahydrofuran; water / 0 °C View Scheme

benzaldehyde (100-52-7) → (2S)-benzylsuccinic acid (3972-36-9)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: sodium methylate / methanol / 0.5 h / Large scale 1.2: Large scale 1.3: Large scale 2.1: Ru(OCOCH3)2{(S)-2,2'-bis(diphenylphosphino)-1,1'-dinaphthyl)}; hydrogen / methanol / 10 h / 50 °C / 760.05 Torr / Molecular sieve; Inert atmosphere; Large scale View Scheme

cis-hexahydroisoindoline (1470-99-1, 1220913-24-5) + (2S)-benzylsuccinic acid (3972-36-9) → mitiglinide (145375-43-5)

Conditions	Yield
Stage #1: (2S)-benzylsuccinic acid With 1H-imidazole; thionyl chloride; triethylamine In ethyl acetate at -10 - -5℃; for 6h; Stage #2: cis-hexahydroisoindoline In ethyl acetate at 20℃; for 18h;	87%

2-(Trimethylsilyl)ethanol (2916-68-9) + (2S)-benzylsuccinic acid (3972-36-9) → (S)-2-Benzyl-succinic acid bis-(2-trimethylsilanyl-ethyl) ester (182247-47-8)

Conditions	Yield
With dmap; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine In dichloromethane

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + (2S)-benzylsuccinic acid (3972-36-9) → (S)-2-Benzyl-succinic acid bis-(2,5-dioxo-pyrrolidin-1-yl) ester

Conditions	Yield
With thionyl chloride; triethylamine 1.) CH2Cl2, 0 deg C, 1 h, 2.) CH2Cl2, RT, overnight; Yield given. Multistep reaction;

4-nitro-phenol (100-02-7) + (2S)-benzylsuccinic acid (3972-36-9) → (S)-2-Benzyl-succinic acid bis-(4-nitro-phenyl) ester (157060-06-5)

Conditions	Yield
With thionyl chloride; triethylamine 1.) CH2Cl2, 0 deg C, 1 h, 2.) CH2Cl2, RT, overnight; Yield given. Multistep reaction;

endo-N-hydroxy-5-norbornene-2,3-dicarboxyimide (21715-90-2) + (2S)-benzylsuccinic acid (3972-36-9) → (S)-2-Benzyl-succinic acid 4-((1S,2R,6S,7R)-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl) ester 1-((1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.02,6]dec-8-en-4-yl) ester (204187-32-6)

Conditions	Yield
With thionyl chloride; triethylamine 1.) CH2Cl2, 0 deg C, 1 h, 2.) CH2Cl2, RT, overnight; Yield given. Multistep reaction;

(2S)-benzylsuccinic acid (3972-36-9) + benzotriazol-1-ol (2592-95-2) → (S)-2-Benzyl-succinic acid dibenzotriazol-1-yl ester

Conditions	Yield
With thionyl chloride; triethylamine 1.) CH2Cl2, 0 deg C, 1 h, 2.) CH2Cl2, RT, overnight; Yield given. Multistep reaction;

(2S)-benzylsuccinic acid (3972-36-9) → (S)-2-benzyl-butan-1,4-diol (190185-60-5)

Conditions	Yield
With borane-THF

methanol (67-56-1) + (2S)-benzylsuccinic acid (3972-36-9) → dimethyl (S)-(-)-benzylsuccinate

Conditions	Yield
With toluene-4-sulfonic acid

(2S)-benzylsuccinic acid (3972-36-9) → (S)-4-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid (113867-24-6)

Conditions	Yield
With sulfuric acid at 20℃; for 8h;
With sulfuric acid In water at 60℃; for 0.333333h;

Upstream product

• 21307-94-8 diethyl (S)-2-benzylsuccinate 
• 5653-88-3 trans-phenylitaconic acid 
• 100-52-7 benzaldehyde 
• 5653-88-3 2-benzylidenesuccinic acid 
• 1141895-98-8 (S)-3-benzyl-4-((R)-4-benzyl-2-oxooxazolidin-3-yl)-4-oxobutanoic acid 
• 136159-65-4 (R)-4-benzyl-3-(3-phenyl-propionyl)-oxazolidin-2-one 
• 21654-18-2 1,4-diethyl 2-benzylsuccinate 
• 35262-43-2 dimethyl 2-benzylsuccinate 
• 215373-19-6 (S)-3-Benzyl-4-oxo-4-((R)-3,3,5-trimethyl-2-oxo-pyrrolidin-1-yl)-butyric acid tert-butyl ester 
• 155956-29-9 (5R)-(-)-(1'-oxo-3'-phenylpropyl)-5,3,3-trimethylpyrrolidin-2-one 
• 131288-25-0 Benzyl (2S)-2-Benzyl-3-t-butoxycarbonyl Propionate 
• 65756-82-3 Z-methyl 4-(phenyl)-3-methoxycarbonylbut-3-enoate 
• 787635-22-7 1,1-dimethylethyl (3S)-4-[(3aS,6R,7aS)-8,8-dimethyl-2,2-dioxidotetrahydro-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-4-oxo-3-(phenylmethyl)butanoate 
• 645-45-4 hydrocinnamic acid chloride 

Downstream Products

• 190185-60-5 (S)-2-benzyl-butan-1,4-diol 
• 145375-43-5 mitiglinide 
• 204187-32-6 (S)-2-Benzyl-succinic acid 4-((1S,2R,6S,7R)-3,5-dioxo-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl) ester 1-((1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl) ester 
• 157060-06-5 (S)-2-Benzyl-succinic acid bis-(4-nitro-phenyl) ester 
• 182247-47-8 (S)-2-Benzyl-succinic acid bis-(2-trimethylsilanyl-ethyl) ester 
• 1220913-25-6 (S)-3-benzyl-4-((3aR,7aS)-1H-isoindol-2(3H,3aH,4H,5H,6H,7H,7aH)-yl)-4-oxobutanoic acid 
• 1651204-34-0 (2S)-2-benzyl-4-[(3aS,7aS)-octahydro-2H-isoindole-2-yl]-4-oxobutanoic acid 
• 865538-96-1 (S)-3-benzyldihydrofuran-2,5-dione 
• 204187-36-0 (S)-2-Benzyl-4-(3aR,7aS)-octahydro-isoindol-2-yl-4-oxo-butyric acid (1R,2S,6R,7S)-3,5-dioxo-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl ester 
• 204187-34-8 (S)-2-Benzyl-4-(3aR,7aS)-octahydro-isoindol-2-yl-4-oxo-butyric acid 4-nitro-phenyl ester 
• 204187-39-3 (S)-2-Benzyl-4-(3aR,7aS)-octahydro-isoindol-2-yl-4-oxo-butyric acid methyl ester 

Relevant articles and documents

Asymmetric hydrogenation of itaconic acids with rhodium(I)-phenyl-CAPP complex; a correction

Asymmetric hydrogenation of itaconic acids 2 under homogeneous catalysis of neutral Rh-complex 3 gives substituted succinic acids 4 of (S)-configuration with > 95% ee.

Preparation method of (S)-2-benzylsuccinic acid

The invention provides a preparation method of (S)-2-benzylsuccinic acid, and relates to a method for preparing (S)-2-benzylsuccinic acid from (R)-2-benzylsuccinic acid. After EDTA is added in an alkaline aqueous solution containing the (R)-2-benzylsuccinic acid, racemization can be implemented effectively. By the method provided by the invention, the (S)-2-benzylsuccinic acid can be prepared from a solution of 2-benzylsuccinic acid (R)-alpha-phenylethanammonium generated in a production process of mitiglinide calcium, and economic benefit is improved further.

Diastereoselective conjugate addition of Grignard reagents to a homochiral fumaramide derived from Oppolzer's sultam

Conjugate addition of Grignard reagents to N,N′-fumaroylbis[(2R)- bornane-10,2-sultam] 1 occurred with moderate to high levels of diastereoselectivity. Diastereomeric excesses were estimated by analysis of the 1H NMR spectra of the succinamide mixtures and enantiomeric excesses from 19F NMR spectra of the bis Mosher esters of the diols produced by reductive cleavage of the succinamides. Saponification of the succinamides gave the corresponding (R)-succinic acids with ees up to 92% showing that addition of the Grignard reagents takes place selectively on the re-face of 1.