3059-97-0

Basic information

• Product Name: D(-)-Isovaline
• Synonyms: (R)-(-)-2-Amino-2-methylbutanoicacidmonohydrate(e.e.);(R)-(-)-2-AMINO-2-METHYLBUTANOIC ACID MONOHYDRATE 99+% (99+% E.E.);(R)-(-)-2-Amino-2-methylbutanoic acid;D(-)-Isovaline;D-ISO-VALINE((R)-2-AMINO-2-METHYLBUTANOIC ACID );(R)-alpha-Ethylalanine (>98%, >99%ee);H-alpha-Et-L-Ala-OH;(2R)-2-Amino-2-methylbutyric acid
• CAS NO: 3059-97-0
• Molecular Formula: C₅H₁₁NO₂
• Molecular Weight: 117.15
• Product Categories: Amino Acid Derivatives;Valine [Val, V];unnatural amino acids;α-Methyl Amino Acids
• Mol File: 3059-97-0.mol
• Article Data: 19

Chemical Properties

• Melting Point: 276-278°C
• Boiling Point: 213.6 °C at 760 mmHg
• Flash Point: 83 °C
• Appearance: White/Needles or Crystalline Powder
• Density: 1.07 g/cm³
• Vapor Pressure: 0.0633mmHg at 25°C
• Refractive Index: 1.465
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 2.38±0.10(Predicted)
• Water Solubility: freely soluble
• CAS DataBase Reference: D(-)-Isovaline(CAS DataBase Reference)
• NIST Chemistry Reference: D(-)-Isovaline(3059-97-0)
• EPA Substance Registry System: D(-)-Isovaline(3059-97-0)

Safety Data

• Safety Statements: 24/25
• TSCA: No
• Hazardous Substances Data: 3059-97-0(Hazardous Substances Data)

Usage

InChI:InChI=1/C5H11NO2/c1-3-5(2,6)4(7)8/h3,6H2,1-2H3,(H,7,8)/t5-/m1/s1

Synthetic route

benzyl (R)-2-azido-2-methylbutanoate (1092559-79-9) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With 1% Pd/C; hydrogen In methanol at 20℃;	100%
With 10% Pd/C; hydrogen In ethanol at 20℃; optical yield given as %ee;	97%

(2R)-2-benzamido-2-methylbutanoic acid (2583-48-4) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With hydrogenchloride at 100℃; for 16h;	99%

(2R)-2-ethoxycarbonylamino-2-methylbutyronitrile → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With hydrogenchloride; methyloxirane	93%

(3R,6S)-3-Ethyl-6-isopropyl-3-methyl-5-phenyl-3,6-dihydro-2H-1,4-oxazin-2-one → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With hydrogenchloride; water at 150℃; for 24h;	89%

(R)-2-Amino-2-methyl-butyric acid ethyl ester (40916-97-0) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With water; sodium hydroxide In ethanol for 4h; Reflux;	89%

(R)-2-amino-2-methylbutanoic acid tert-butyl ester → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Stage #1: (R)-2-amino-2-methylbutanoic acid tert-butyl ester With methanesulfonic acid In 1,2-dichloro-ethane at 25 - 80℃; for 13h; Stage #2: With triethylamine In 1,2-dichloro-ethane at 25℃; for 16h;	76%

(+/-)-2-amino-4-(benzylthio)-2-methylbutanoic acid (88082-98-8) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With ranney nickel In water for 12h; Heating;	71%

N-chloroacetyl-D-isovaline (86960-59-0) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With hydrogenchloride

DL-isovaline (595-39-1) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
durch Vergaerung mit Hefe unter Zusatz von Zucker;
Multi-step reaction with 2 steps 1: Ac2O 2: HCl / methanol View Scheme

4-ethyl-4-methyl-2-phenyl-4H-oxazol-5-one (2576-61-6) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
(i) (racemate resolution using l-menthol), (ii) aq. HBr; Multistep reaction;
Multi-step reaction with 2 steps 1: (i) Na, benzene, (ii) /BRN= 155858/ 2: aq. HBr / Heating View Scheme

2-Benzamido-2-methyl-buttersaeure-l-menthylester → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With hydrogen bromide Heating;

(R)-2-Formylamino-2-methyl-butyric acid → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With hydrogenchloride In methanol

ethyl bromide (74-96-4) + L-Alanine methyl ester (10065-72-2) + trimethoxonium tetrafluoroborate (420-37-1) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Yield given. Multistep reaction;

(RS)-2-amino-2-methylbutanamide (59209-90-4) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0) + L-isovaline (595-40-4)

Conditions	Yield
at 37℃; Mycobacterium neoaurum ATCC 25795, pH 8-8.5; Yield given. Title compound not separated from byproducts;

(R)-2-Methyl-2-((R)-2-phenoxy-3-phenyl-propionylamino)-butyric acid → (2R)-2-amino-2-methylbutanoic acid (3059-97-0) + (R)-2-phenoxy-3-phenylpropionic acid (64682-83-3, 120346-42-1)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 110℃;

(R)-2-Methyl-2-((R)-2-phenoxy-3-phenyl-propionylamino)-butyric acid tert-butyl ester → (2R)-2-amino-2-methylbutanoic acid (3059-97-0) + (R)-2-phenoxy-3-phenylpropionic acid (64682-83-3, 120346-42-1)

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water at 110℃;

(2R,3R)-2-Amino-3-hydroxy-2-methyl-butyric acid; hydriodide → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With phosphorus; hydrogen iodide In water at 160℃; for 5.5h; freeing from HI salt with Dowex 50 W*8;

(R)-2-Methyl-2-(2,2,2-trichloro-acetylamino)-butyric acid (177273-84-6) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
With potassium hydroxide at 50℃;

dl-isovaline → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
ueber das Chininsalz der Formylverbindung;
ueber das Brucinsalz der Formylverbindung;

2-amino-2-methyl-butyric acid isopropyl ester; hydrochloride → (2R)-2-amino-2-methylbutanoic acid (3059-97-0) + L-isovaline (595-40-4)

Conditions	Yield
With hydrogenchloride Heating;

(Z)-1-iodo-2-methyl-1-butene (52812-57-4) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 6 steps 1: 1.) n-BuLi, 1/2CuBr-Me2S 2: DBU / CH2Cl2 / 1 h / -78 °C 3: 60 percent / xylene / 4 h / 140 °C 4: 81 percent / O3, Me2S / 12 h 5: Jones reagent / 0.33 h 6: KOH / 50 °C View Scheme

2,2,2-Trichloro-N-((R)-1-formyl-1-methyl-propyl)-acetamide (177273-81-3) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Jones reagent / 0.33 h 2: KOH / 50 °C View Scheme

2,2,2-Trichloro-N-((E)-(1R,4S)-1-ethyl-4-methoxymethoxy-1,5-dimethyl-hex-2-enyl)-acetamide → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 81 percent / O3, Me2S / 12 h 2: Jones reagent / 0.33 h 3: KOH / 50 °C View Scheme

2,2,2-Trichloro-acetimidic acid (Z)-(S)-1-((S)-1-methoxymethoxy-2-methyl-propyl)-3-methyl-pent-2-enyl ester → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 60 percent / xylene / 4 h / 140 °C 2: 81 percent / O3, Me2S / 12 h 3: Jones reagent / 0.33 h 4: KOH / 50 °C View Scheme

(Z)-(3S,4S)-3-Methoxymethoxy-2,6-dimethyl-oct-5-en-4-ol → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: DBU / CH2Cl2 / 1 h / -78 °C 2: 60 percent / xylene / 4 h / 140 °C 3: 81 percent / O3, Me2S / 12 h 4: Jones reagent / 0.33 h 5: KOH / 50 °C View Scheme

(2R,5R)-2-(t-Butyl)-5-ethyl-3,5-dimethyl-4-oxo-1-imidazolidincarbonsaeure-t-butylester (152033-17-5) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) 6N HCl; 2.) 1N NaOH / 1.) methanol, 24 h, reflux; 2.) 16 h 2: 90 percent / 4 N HCl / dioxane / 4 h / 80 °C 3: 99 percent / conc. aq. HCl / 16 h / 100 °C View Scheme

N-benzoyl-D-isovaline-methylamide (161956-11-2) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 90 percent / 4 N HCl / dioxane / 4 h / 80 °C 2: 99 percent / conc. aq. HCl / 16 h / 100 °C View Scheme

(R)-2-Methyl-2-((3R,4S)-2-oxo-3-phenoxy-4-phenyl-azetidin-1-yl)-butyric acid → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: Li/NH3 / tetrahydrofuran; 2-methyl-propan-2-ol 2: 6 N hydrochloric acid / tetrahydrofuran; H2O / 110 °C View Scheme

(R)-2-Methyl-2-((3R,4S)-2-oxo-3-phenoxy-4-phenyl-azetidin-1-yl)-butyric acid tert-butyl ester (110510-47-9) → (2R)-2-amino-2-methylbutanoic acid (3059-97-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: CF3COOH 2: Li/NH3 / tetrahydrofuran; 2-methyl-propan-2-ol 3: 6 N hydrochloric acid / tetrahydrofuran; H2O / 110 °C View Scheme
Multi-step reaction with 2 steps 1: H2 / Pd-C 2: 6 N hydrochloric acid / tetrahydrofuran; H2O / 110 °C View Scheme

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + di-tert-butyl dicarbonate (24424-99-5) → (R)-2-((tert-butoxycarbonyl)amino)-2-methylbutanoic acid (123254-58-0)

Conditions	Yield
With triethylamine In tetrahydrofuran Inert atmosphere;	97%

2,6-Dichloropyrimidine (3934-20-1) + (2R)-2-amino-2-methylbutanoic acid (3059-97-0) → (R)-2-((2-chloropyrimidin-4-yl)amino)-2-methylbutanoic acid

Conditions	Yield
With potassium carbonate In isopropyl alcohol at 90℃; for 5.5h;	93%

methanol (67-56-1) + (2R)-2-amino-2-methylbutanoic acid (3059-97-0) → methyl (R)-2-amino-2-methyl-butyrate hydrochloride (118725-00-1)

Conditions	Yield
With thionyl chloride for 3h; Reflux;	93%

potassium cyanate (590-28-3) + (2R)-2-amino-2-methylbutanoic acid (3059-97-0) → (5R)-5-ethyl-5-methyl-imidazolidine-2,4-dione

Conditions	Yield
Stage #1: potassium cyanate; (2R)-2-amino-2-methylbutanoic acid In water at 90℃; for 3h; Stage #2: With hydrogenchloride In water at 90℃; for 2h;	91%
Stage #1: potassium cyanate; (2R)-2-amino-2-methylbutanoic acid In water at 90℃; for 2h; Stage #2: With hydrogenchloride In water at 90℃; for 1h;	76%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 4-bromophenyl isocyanate (2493-02-9) → N-[(4-bromophenyl)carbamoyl]-D-isovaline

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃;	85%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 1-fluoro-3-isocyanatobenzene (404-71-7) → N-[(3-fluorophenyl)carbamoyl]-D-isovaline

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃; for 3h;	77%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + p-chlorphenylisocyanate (104-12-1) → N-[(4-chlorophenyl)carbamoyl]-D-isovaline

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃; for 4.5h;	77%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 4-amino-5-chloro-2-ethoxybenzoic acid (108282-38-8) → (+)-N-(4-amino-5-chloro-2-ethoxybenzoyl)-L-isovaline

Conditions	Yield
With triethylamine; HATU In N,N-dimethyl-formamide at 50℃; for 5h;	74%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + m-chlorophenyl isocyanate (2909-38-8) → N-[(3-chlorophenyl)carbamoyl]-D-isovaline

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃; for 2h;	71%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 4-amino 5-bromo 2-methoxy benzoic acid (35290-97-2) → (+)-N-(4-amino-5-bromo-2-methoxybenzoyl)-L-isovaline

Conditions	Yield
With triethylamine; HATU In N,N-dimethyl-formamide at 50℃; for 5h;	71%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 1-isocyanato-4-trifluoromethoxy-benzene (35037-73-1) → (-)-N-{[4-(trifluoromethoxy)phenyl]carbamoyl}-D-isovaline

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃;	68%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 1-(difluoromethoxy)-4-isocyanatobenzene (58417-15-5) → N-{[4-(difluoromethoxy)phenyl]carbamoyl}-D-isovaline

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃; for 3.5h;	64%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 1-iodo-4-isocyanatobenzene (15845-62-2) → N-[(4-iodophenyl)carbamoyl]-D-isovaline

Conditions	Yield
With sodium hydroxide In dichloromethane at 20℃;	62%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 4-amino-2-ethoxy-5-fluorobenzoic acid → (+)-N-(4-amino-2-ethoxy-5-fluorobenzoyl)-L-isovaline

Conditions	Yield
With triethylamine; HATU In N,N-dimethyl-formamide at 50℃; for 5h;	40%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 4-amino-5-chloro-2-methoxybenzoic acid (7206-70-4) → (+)-N-(4-amino-5-chloro-2-methoxybenzoyl)-L-isovaline

Conditions	Yield
Stage #1: 4-amino-5-chloro-2-methoxybenzoic acid With triethylamine; HATU In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: (2R)-2-amino-2-methylbutanoic acid In N,N-dimethyl-formamide at 50℃; for 3h;	33%

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) + 1-Bromo-3-iodobenzene (591-18-4) → (R)-2-((3-bromophenyl)amino)-2-methylbutanoic acid

Conditions	Yield
With copper(l) iodide; caesium carbonate In N,N-dimethyl-formamide at 80℃; for 8h;	27.02%

carbon disulfide (75-15-0) + ethyl bromide (74-96-4) + (2R)-2-amino-2-methylbutanoic acid (3059-97-0) → (R)-N-Dithiocarbethoxyisovalin (27539-03-3)

Conditions	Yield
(i) aq. K2CO3, EtOH, (ii) /BRN= 1209224/; Multistep reaction;

(2R)-2-amino-2-methylbutanoic acid (3059-97-0) → (R)-2-amino-2-methylbutan-1-ol (10196-30-2)

Conditions	Yield
(i) EtOH, SOCl2, (ii) NaBH4; Multistep reaction;

Upstream product

• 40916-97-0 (R)-2-Amino-2-methyl-butyric acid ethyl ester 
• 123254-58-0 (R)-2-((tert-butoxycarbonyl)amino)-2-methylbutanoic acid 
• 1092559-79-9 benzyl (R)-2-azido-2-methylbutanoate 
• 88050-50-4 (3R,6S)-3-(2-benzylthioethyl)-6-isopropyl-2,5-dimethoxy-3-methyl-3,6-dihydropyrazine 
• 88050-51-5 methyl (R)-2-amino-4-benzylthio-2-methylbutanoate 
• 110510-47-9 (R)-2-Methyl-2-((3R,4S)-2-oxo-3-phenoxy-4-phenyl-azetidin-1-yl)-butyric acid tert-butyl ester 
• 161956-11-2 N-benzoyl-D-isovaline-methylamide 
• 152033-17-5 (2R,5R)-2-(t-Butyl)-5-ethyl-3,5-dimethyl-4-oxo-1-imidazolidincarbonsaeure-t-butylester 

Downstream Products

• 73473-40-2 (2R)-2-amino-2-methylbutanoic acid hydrochloride 
• 16820-12-5 (5R)-5-ethyl-5-methylimidazolidine-2,4-dione 
• 123254-58-0 (R)-2-((tert-butoxycarbonyl)amino)-2-methylbutanoic acid 

Relevant articles and documents

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High-chirality method for selectively synthesizing alpha-disubstituted alpha-amino acid

The invention discloses a high-chirality method for selectively synthesizing alpha-disubstituted alpha-amino acid. The high-chirality method for selectively synthesizing alpha-disubstituted alpha-amino acid is characterized by comprising the following steps: step one, reacting S-tert-butanesulfinyl amide or R-tert-butanesulfinyl amide, R-beta substituted ethyl pyruvate and tetraethyl titanate in atetrahydrofuran solvent to obtain a compound C; step two, reacting the compound C with alkyl substituted magnesium bromide under the catalyzing effect of zinc dimethyl in tetrahydrofuran to obtain acompound E; step three, reacting the compound E under the effect of ammonium chloride and anhydrous hydrogen chloride to obtain a compound F; and step four, hydrolyzing the compound F in an ethanol aqueous solution of sodium hydroxide to obtain hydrochloride of a compound G, and carrying out ion exchange to obtain the compound G. The chiral selective reaction is greatly improved, and the method issimple in process, uses cheap and easily obtained raw materials, is simple and convenient to operate, is quite suitable for industrial mass production, and has quite extensive industrial applicationprospect and market value.

PROCESS FOR PRODUCING SOLID AMINO ACID

The problem to be solved by the present invention is to ea lily and efficiently produce an amino acid having 2 to 7 carbon atoms as a high-purity solid without complicated operation, which is useful as a synthetic intermediate for medicines or agrochemicals. The present invention is characterized in comprising a step of precipitating solid amino acid with high purity. In the present invention, the by-produced salt composed of the sulfonic acid and the amine was removed to the mother liquor by reacting an amine with a sulfonic acid salt of amino acid in an aprotic polar solvent, or by reacting a sulfonic acid with an amine salt of amino acid in an aprotic polar solvent. The sulfonic acid salt of amino acid, for example, may be produced by reacting a N-(tert-butoxycarbonyl) amino acid with a sulfonic acid, or by reacting an amino acid tert-butyl ester with a sulfonic acid.