112111-45-2

Basic information

• Product Name: (R)-(-)-Modafinil Acid
• Synonyms: (R)-Modanifil acid;R-(benzhydryl sulfinyl) acetic acid;(R)-(-)-Modafinic acid;Acetic acid, 2-[(R)-(diphenylmethyl)sulfinyl]-;(R)-(-)-Modafinil Acid;(R)-Modafinil Carboxylate;2-[(R)-(Diphenyl-methyl)sulfinyl]-acetic Acid
• CAS NO: 112111-45-2
• Molecular Formula: C₁₅H₁₄O₃S
• Molecular Weight: 274.339
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Aromatics;Chiral Reagents
• Mol File: 112111-45-2.mol
• Article Data: 9

Chemical Properties

• Melting Point: 118-120℃
• Boiling Point: 539.2 °C at 760 mmHg
• Flash Point: 279.9 °C
• Appearance: off-white solid
• Density: 1.327
• Vapor Pressure: 1.86E-12mmHg at 25°C
• Refractive Index: 1.648
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.83±0.10(Predicted)
• CAS DataBase Reference: (R)-(-)-Modafinil Acid(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-(-)-Modafinil Acid(112111-45-2)
• EPA Substance Registry System: (R)-(-)-Modafinil Acid(112111-45-2)

Safety Data

• Hazardous Substances Data: 112111-45-2(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

(R)-Modafinil Acid is used for treatment of human or animal oligospermia and ovum-deficient disease.

InChI:InChI=1/C15H14O3S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H,16,17)/t19-/m1/s1

Synthetic route

(benzhydrylthio)acetic acid (63547-22-8) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
With NADP; sodium hydroxide In isopropyl alcohol at 35℃; pH=8.54; Catalytic behavior; Concentration; Solvent; Reagent/catalyst; Temperature; pH-value; Alkaline conditions; enantioselective reaction;	100%
Multi-step reaction with 4 steps 1.1: 99 percent / H2SO4 / Heating 2.1: H2SO4; 2-propanol; aq. H2O2 / methanol / 20 °C 3.1: 62.1 g / NaOH; H2O / ethanol / 1 h / 20 °C 4.1: (R)-(+)-α-methylbenzylamine / H2O / Heating 4.2: aq. HCl / pH 2 View Scheme

2-((R)-Diphenyl-methanesulfinyl)-1-((R)-4-phenyl-2-thioxo-thiazolidin-3-yl)-ethanone (827603-84-9) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran; water at 0 - 20℃;	96%

Λ-[Ru(2,2-bipyridine)2((diphenylmethanesulfinyl)acetic acid-H)](PF6) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
With trifluoroacetic acid In acetonitrile at 60℃; for 3h; Inert atmosphere; enantioselective reaction;	84%

modafinil acid (63547-24-0) → (R)-Modafinil acid (112111-45-2) + (+)-(S)-(diphenylmethanesulfinyl)acetic acid (112111-44-1)

Conditions	Yield
Stage #1: modafinil acid With (S)-1-phenyl-ethylamine In water Heating; Stage #2: With hydrogenchloride pH=2;	A 12.6 g B n/a
Stage #1: modafinil acid With (R)-1-phenyl-ethyl-amine In water Heating; Stage #2: With hydrogenchloride pH=2;	A n/a B 17.0 g

modafinil acid (63547-24-0) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 44.5 percent / 4-(dimethylamino)pyridine; 1,3-dicyclohexylcarbodiimide / CH2Cl2 2: 96 percent / lithium hydroxide / tetrahydrofuran; H2O / 0 - 20 °C View Scheme

1,1-Diphenylmethanol (91-01-0) + BF3(C2H5)2O → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: 99 percent / trifluoroacetic acid / 3 h / 20 °C 2.1: 99 percent / H2SO4 / Heating 3.1: H2SO4; 2-propanol; aq. H2O2 / methanol / 20 °C 4.1: 62.1 g / NaOH; H2O / ethanol / 1 h / 20 °C 5.1: (R)-(+)-α-methylbenzylamine / H2O / Heating 5.2: aq. HCl / pH 2 View Scheme

(diphenylmethyl)(ethyl acetate)sulfide (63547-23-9) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: H2SO4; 2-propanol; aq. H2O2 / methanol / 20 °C 2.1: 62.1 g / NaOH; H2O / ethanol / 1 h / 20 °C 3.1: (R)-(+)-α-methylbenzylamine / H2O / Heating 3.2: aq. HCl / pH 2 View Scheme

(diphenylmethyl)(ethyl acetate)sulfoxide (118286-19-4) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 62.1 g / NaOH; H2O / ethanol / 1 h / 20 °C 2.1: (R)-(+)-α-methylbenzylamine / H2O / Heating 2.2: aq. HCl / pH 2 View Scheme

(-)-α-methylbenzylamine (2627-86-3) + modafinil acid (63547-24-0) → (S)-modafinic acid*(S)-α-methylbenzylamine (949092-13-1) + (R)-Modafinil acid (112111-45-2)

Conditions	Yield
In isopropyl alcohol at 20℃; Product distribution / selectivity; Heating / reflux;
In ethyl acetate at 20℃; Product distribution / selectivity; Heating / reflux;
In N,N-dimethyl-formamide; acetone at 20℃; Product distribution / selectivity; Heating / reflux;

(benzhydrylthio)acetic acid (63547-22-8) → (R)-Modafinil acid (112111-45-2) + (+)-(S)-(diphenylmethanesulfinyl)acetic acid (112111-44-1)

Conditions	Yield
With 3-butyl-1-methyl-1H-imidazol-3-ium hexafluorophosphate In tetrachloromethane at 20℃; for 48h; Title compound not separated from byproducts.;
Stage #1: (benzhydrylthio)acetic acid With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 0 - 5℃; for 0.5h; Stage #2: With (1S)-(+)-(10-camphorsulfonyl)-oxaziridine In toluene at 25 - 30℃;

(+)-(S)-(diphenylmethanesulfinyl)acetic acid (112111-44-1) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
In dimethyl sulfoxide at 90℃; for 17h; Product distribution / selectivity;
In N,N-dimethyl-formamide at 90℃; for 17h; Product distribution / selectivity;

2-(benzhydrylsulfinyl)acetic acid (-)-α-methylbenzylamine (112245-25-7) → (R)-Modafinil acid (112111-45-2)

Conditions	Yield
With hydrogenchloride In water at 20℃;

methyl iodide (74-88-4) + (R)-Modafinil acid (112111-45-2) → (R)-(-)-methyl (diphenylmethanesulfinyl)-acetate (713134-72-6)

Conditions	Yield
With potassium carbonate In acetone Reflux;	70%
With potassium carbonate In acetone Heating;	68%
With potassium carbonate In acetone for 4h; Reflux;

(R)-Modafinil acid (112111-45-2) → Nuvigil (112111-43-0)

Conditions	Yield
With Bacillus subtilis var. niger IFO-3180 In N,N-dimethyl-formamide at 28℃; for 168h;	60%
Multi-step reaction with 2 steps 1: 68 percent / K2CO3 / acetone / Heating 2: 55 percent / aq. NH4OH; NH4Cl / methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetone / Reflux 2: ammonium hydroxide; ammonium chloride / methanol / 20 °C View Scheme
Stage #1: (R)-Modafinil acid With methanol; thionyl chloride at 0 - 20℃; for 3h; Stage #2: With ammonium hydroxide In methanol; water at 0℃; Reagent/catalyst; Temperature; Time;

methanol (67-56-1) + (R)-Modafinil acid (112111-45-2) → (R)-(-)-methyl (diphenylmethanesulfinyl)-acetate (713134-72-6)

Conditions	Yield
With hydrogenchloride In water at 20℃; for 1 - 24h; Product distribution / selectivity; Heating / reflux;
With thionyl chloride at 0 - 20℃; for 3 - 20h; Product distribution / selectivity;

(R)-Modafinil acid (112111-45-2) → (+)-(S)-(diphenylmethanesulfinyl)acetic acid (112111-44-1)

Conditions	Yield
Stage #1: (R)-Modafinil acid With indium; pivaloyl chloride In isopropyl alcohol at 15 - 30℃; for 3h; Stage #2: With hydrogenchloride In water; isopropyl alcohol at 20℃; for 0.5h; Product distribution / selectivity;
With perchloric acid; sodium bromide In water; ethyl acetate at 20℃; for 20h; Product distribution / selectivity;
With perchloric acid; sodium bromide In water; acetonitrile at 20℃; for 20h; Product distribution / selectivity;

isobutyl chloroformate (543-27-1) + (R)-Modafinil acid (112111-45-2) → C20H22O5S

Conditions	Yield
Stage #1: (R)-Modafinil acid With triethylamine In dichloromethane at 5 - 30℃; for 0.5h; Stage #2: isobutyl chloroformate In dichloromethane at 0 - 25℃; for 3.25h;

Upstream product

• 112245-25-7 2-(benzhydrylsulfinyl)acetic acid (-)-α-methylbenzylamine 
• 112111-44-1 (S)-(+)-(diphenylmethanesulfinyl)acetic acid 
• 63547-22-8 (benzhydrylthio)acetic acid 
• 2627-86-3 (-)-α-methylbenzylamine 
• 63547-24-0 modafinil acid 
• 118286-19-4 (diphenylmethyl)(ethyl acetate)sulfoxide 
• 63547-23-9 (diphenylmethyl)(ethyl acetate)sulfide 
• 91-01-0 1,1-Diphenylmethanol 
• 827603-84-9 2-((R)-Diphenyl-methanesulfinyl)-1-((R)-4-phenyl-2-thioxo-thiazolidin-3-yl)-ethanone 

Downstream Products

• 112111-44-1 (S)-(+)-(diphenylmethanesulfinyl)acetic acid 
• 713134-72-6 (R)-(-)-methyl (diphenylmethanesulfinyl)-acetate 
• 112111-43-0 Nuvigil 

Relevant articles and documents

Biocatalysts and methods for the synthesis of armodafinil

The present invention relates to non-naturally occurring polypeptides useful for preparing armodafinil, polynucleotides encoding the polypeptides, and methods of using the polypeptides. The non-naturally occurring polypeptides of the present invention are effective in carrying out biocatalytic conversion of the (i) 2-(benzhydrylsulfinyl)acetamide to (?)-2-[(R)-(diphenyl-methyl)sulfinyl]acetamide (armodafinil), or (ii) benzhydryl-thioacetic acid to (R)-2-(benzhydrylsulfinyl)acetic acid, which is a pivotal intermediate in the synthesis of armodafinil, in enantiomeric excess.

NOVEL CRYSTALLINE POLYMORPH OF ARMODAFINIL AND AN IMPROVED PROCESS FOR PREPARATION THEREOF

The present invention relates to a novel crystalline polymorph of armodafinil. In another aspect the invention relates to an improved process for preparation of the novel polymorph of armodafinil.

A PROCESS OF SULFOXIDATION OF BIOLOGICALLY ACTIVE COMPOUNDS

The present invention relates to a new process for the preparation of sulfoxides, preferably stereoselective preparation of substituted or unsubstituted chiral sulfinyl derivatives 2-(2- pyridylmethyl) sulfinyl-l H-benzimidazole by oxidation with oxaziridine in presence of suitable solvent and base.