99-15-0

Basic information

• Product Name: Acetylleucine
• Synonyms: IFLAB-BB F0777-0821;acetylleucine;ACETYL-DL-LEUCINE;ACETYL-DL-LEUCINE, N-;AC-DL-LEU-OH;AKOS BBS-00004735;N-ACETYL-DL-LEU;N-ACETYL-DL-LEUCINE
• CAS NO: 99-15-0
• Molecular Formula: C₈H₁₅NO₃
• Molecular Weight: 173.21
• EINECS: 202-734-9
• Product Categories: Amino Acids Derivatives;Amino Acids;Amino Acid Derivatives;Leucine [Leu, L];Amino Acids and Derivatives;Ac-Amino Acids;Amino Acids (N-Protected);Biochemistry;Amino Acid Derivatives;A - H;Amino Acids;Modified Amino Acids;TANGANIL
• Mol File: 99-15-0.mol
• Article Data: 18

Chemical Properties

• Melting Point: 160°C
• Boiling Point: 369.7 °C at 760 mmHg
• Flash Point: 177.4 °C
• Appearance: white powder
• Density: 1.069 g/cm³
• Storage Temp.: −20°C
• Solubility: almost transparency in EtOH
• PKA: 3.67±0.10(Predicted)
• CAS DataBase Reference: Acetylleucine(CAS DataBase Reference)
• NIST Chemistry Reference: Acetylleucine(99-15-0)
• EPA Substance Registry System: Acetylleucine(99-15-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 99-15-0(Hazardous Substances Data)

Usage

Uses

antivertigo

World Health Organization (WHO)

The products were indicated for the treatment of vertigo and had been authorized for marketing under the "grandfather" clause, which waives full registration requirements for products marketed before 1963.

InChI:InChI=1/C8H15NO3/c1-5(2)4-7(8(11)12)9-6(3)10/h5,7H,4H2,1-3H3,(H,9,10)(H,11,12)

Synthetic route

acetamide (60-35-5) + carbon monoxide (201230-82-2) + isovaleraldehyde (590-86-3) → N-acetylleucine (99-15-0)

Conditions	Yield
With sulfuric acid; lithium bromide; bis(triphenylphosphine)palladium dibromide In various solvent(s) at 120℃; under 45003.6 Torr; for 12h;	99%
With 1-methyl-pyrrolidin-2-one; sulfuric acid; lithium bromide; palladium on activated charcoal at 100℃; under 45003.6 Torr; for 12h;	75%
With sulfuric acid; triphenylphosphine; lithium bromide; palladium on activated charcoal In 1-methyl-pyrrolidin-2-one; toluene at 90℃; under 45003.6 Torr; for 16h;	64.4%
With 3-ethyl-1-methyl-1H-imidazol-3-ium bromide; triphenylphosphine; palladium(II) bromide at 100℃; under 45004.5 Torr; for 15h;	63%
With hydrogenchloride; potassium tetrachloroplatinate; triphenylphosphine In 1,4-dioxane at 120℃; under 45600 Torr; for 15h;	44%

L-leucine (61-90-5) + acetic acid (64-19-7) → N-acetylleucine (99-15-0)

Conditions	Yield
at 150℃; microwave irradiation;	94%

acetamide (60-35-5) + carbon monoxide (201230-82-2) + isobutene (115-11-7) → N-acetylleucine (99-15-0)

Conditions	Yield
With carbonylhydridetris(triphenylphosphine)rhodium(I); dicobalt octacarbonyl; hydrogen In ethyl acetate at 120℃; for 4h;	84%

acetamide (60-35-5) + 2-methyl-1-buten-4-ol (763-32-6) + carbon monoxide (201230-82-2) → N-acetylleucine (99-15-0)

Conditions	Yield
With hydrogen; carbonylhydridetris(triphenylphosphine)rhodium(I); dicobalt octacarbonyl In 1,4-dioxane at 100℃; under 100 Torr; for 12h;	62%
With hydrogen; dicobalt octacarbonyl; Co-catalyst In 1,4-dioxane at 110℃; under 60800 - 83600.1 Torr;	34%

acetamide (60-35-5) + carbon monoxide (201230-82-2) + 3-methyl-2-buten-1-ol (556-82-1) → N-acetylleucine (99-15-0)

Conditions	Yield
With hydrogen; carbonylhydridetris(triphenylphosphine)rhodium(I); dicobalt octacarbonyl In 1,4-dioxane at 110℃; under 60800 - 83600.1 Torr; for 12h;	62%

Ketene (463-51-4) + L-leucine (61-90-5) → N-acetylleucine (99-15-0)

Conditions	Yield
With water
is sauer Loesung;

acetylamino-isobutyl-malonic acid (408536-45-8) → N-acetylleucine (99-15-0)

DL-leucine ethyl ester (2899-43-6) + acetic anhydride (108-24-7) → N-acetylleucine (99-15-0)

Conditions	Yield
durch nachfolgende Verseifung mit Natronlauge;

acetic anhydride (108-24-7) + LEUCINE (328-39-2) → N-acetylleucine (99-15-0)

Conditions	Yield
With sodium hydroxide l(-)-acetylleucine;
With sodium hydrogencarbonate In 1,4-dioxane; water Ambient temperature; Yield given;

acetic acid (64-19-7) + LEUCINE (328-39-2) → N-acetylleucine (99-15-0)

Ketene (463-51-4) + LEUCINE (328-39-2) → N-acetylleucine (99-15-0)

Conditions	Yield
With water
With water l(-)-acetylleucine;

acetamide (60-35-5) + carbon monoxide (201230-82-2) + 3-methyl-2-buten-1-ol (556-82-1) → N-acetylleucine (99-15-0) + 2-acetamido-4-methylhexanoic acid (757959-97-0) + 2-acetamido-5-methylhexanoic acid (5440-33-5)

Conditions	Yield
With hydrogen; carbonylhydridetris(triphenylphosphine)rhodium(I); dicobalt octacarbonyl In 1,4-dioxane Product distribution; Mechanism; 100 atm, 25 deg C and 120 deg C, 16 h, then 130 atm 2 to 3 h; reactions of derivatives;
With hydrogen; carbonylhydridetris(triphenylphosphine)rhodium(I); dicobalt octacarbonyl In 1,4-dioxane 100 atm, 25 deg C and 120 deg C, 16 h, then 130 atm 2 to 3 h; Yield given. Yields of byproduct given;

acetamide (60-35-5) + 3,10-diethyl-3,6,10-trimethyl-4,9-dioxa-3,10-disiladodecane (105746-99-4) + 3-methyl-2-buten-1-ol (556-82-1) → N-acetylleucine (99-15-0) + 2-acetamido-4-methylhexanoic acid (757959-97-0) + 2-acetamido-5-methylhexanoic acid (5440-33-5)

Conditions	Yield
With hydrogen; carbonylhydridetris(triphenylphosphine)rhodium(I); dicobalt octacarbonyl In 1,4-dioxane 100 atm, 25 deg C and 120 deg C, 16 h, then 130 atm 2 to 3 h; Yield given. Yields of byproduct given;

2-Acetamidoacrylic acid (5429-56-1) + isopropylmercury(II) chloride (30615-19-1) → N-acetylleucine (99-15-0)

Conditions	Yield
With sodium tetrahydroborate; triphenylphosphine; trifluoroacetic acid; Wang resin; diethylazodicarboxylate 1.) THF, 24 h, RT; 2.) CH2Cl2, H2O, 90 min, RT; 3.) CH2Cl2, RT, 30 min; Yield given; Multistep reaction;

N-Ac-Leu (1188-21-2) + trifluoroacetic acid (76-05-1) → N-acetylleucine (99-15-0) + (S)-2-(2,2,2-trifluoroacetamido)-4-methylpentanoic acid (1480-30-4) + racemic L-leucine

water (7732-18-5) + 5-ethoxy-4-isobutyl-2-methyl-oxazole; hydrochloride → N-acetylleucine (99-15-0)

N-Ac-Leu (1188-21-2) → N-acetylleucine (99-15-0)

Conditions	Yield
With tricyclohexylphosphine; chloro(1,5-cyclooctadiene)rhodium(I) dimer In acetonitrile at 60℃; for 48h; Racemization;

acetylamino-isobutyl-malonic acid diethyl ester (151962-48-0) → N-acetylleucine (99-15-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq.-ethanolic NaOH View Scheme

ethyl 2-acetamido-2-ethoxycarbonyl-4-methyl-4-pentenoic acid (37944-29-9) → N-acetylleucine (99-15-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: Raney nickel; ethanol 2: aq.-ethanolic NaOH View Scheme

acetyl chloride (75-36-5) + LEUCINE (328-39-2) → N-acetylleucine (99-15-0)

Conditions	Yield
With sodium carbonate In 1,4-dioxane; water at 20℃; Inert atmosphere;

4-nitrophenol acetate (830-03-5) + LEUCINE (328-39-2) → N-acetylleucine (99-15-0)

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; water at 24.84℃; pH=8.5 - 9; Kinetics;

N-acetylleucine (99-15-0) + bis(tri-n-butyltin)oxide (56-35-9) → N-acetyl-DL-CH3CH(CH3)CH2CHNHCOO-tri-n-butyltin (1801-46-3)

Conditions	Yield
byproducts: H2O;	88%
byproducts: H2O;	88%
In toluene byproducts: H2O; azeotropic dehydration with toluene; recrystn. (benzene) or sublimation;

N-hydroxyphthalimide (524-38-9) + N-acetylleucine (99-15-0) → 1,3-dioxoisoindolin-2-yl acetylleucinate (97433-42-6)

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 1h;	80%

formaldehyd (50-00-0) + N-acetylleucine (99-15-0) → 3-Acetyl-4-isobutyl-5-oxazolidinone (150577-30-3)

Conditions	Yield
With toluene-4-sulfonic acid In benzene	72%
With diethyldichlorosilane Heating;	60%

betahistine (5638-76-6) + N-acetylleucine (99-15-0) → (S)-2-Acetylamino-4-methyl-pentanoic acid methyl-(2-pyridin-2-yl-ethyl)-amide

Conditions	Yield
With dicyclohexyl-carbodiimide at 20℃; Condensation;	70%

N-acetylleucine (99-15-0) + propargyl bromide (106-96-7) → N-acetylleucine propargyl ester

Conditions	Yield
Stage #1: N-acetylleucine With potassium carbonate Stage #2: propargyl bromide	65%

C6H4NCH2CHCCH2 (491-35-0) + N-acetylleucine (99-15-0) → C17H22N2O

Conditions	Yield
With ammonium peroxydisulfate; [4,4’-bis(1,1-dimethylethyl)-2,2’-bipyridine-N1,N1‘]bis [3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]iridium(III) hexafluorophosphate In dimethyl sulfoxide at 20℃; Irradiation; Inert atmosphere;	61%

N-acetylleucine (99-15-0) + acetic anhydride (108-24-7) → Acetic acid (2R,4R)-4-isobutyl-2-methyl-3-nitro-5-oxo-oxazolidin-2-yl ester (130668-74-5)

Conditions	Yield
With nitric acid 1.) -20 deg C, 10 min, 2.) -20 deg C to 0 deg C, 5 min;	50%

N-acetylleucine (99-15-0) + acetic anhydride (108-24-7) → N-(5-methyl-2-oxohexan-3-yl)acetamide (30057-77-3)

Conditions	Yield
Stage #1: N-acetylleucine; acetic anhydride With dmap; triethylamine at 20℃; Stage #2: With acetic acid at 20℃; for 0.5h;	48%

N-acetylleucine (99-15-0) → L-leucine (61-90-5)

Conditions	Yield
With sodium hydroxide; acylase Amano 30000 from Aspergillus spp. (30 u/mg); water; cobalt(II) chloride at 37 - 40℃; for 48h;	39%
Herstellung mit Hilfe eines Enzym-Praeparats aus Aspergillus und Penicillium;

N-acetylleucine (99-15-0) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → [4-Isobutyl-5-oxo-oxazolidin-(2Z)-ylidene]-acetaldehyde

Conditions	Yield
With trichlorophosphate at 90℃;	35%

N-acetylleucine (99-15-0) + O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (94790-37-1) + 11-amino-23-hydroxycarbonyl-25,27-dihydroxy-26,28-dipropoxypentacyclo[19.3.1.13,7.19,13.115,19]octacosa-1(25),3,5,7(28),9,11,13(27),15,17,19(26),21,23-dodecene (702699-88-5) → 11-[N-acetyl-(dl)-leucyl]amino-23-benzotriazolyloxycarbonyl-25,27-dihydroxy-26,28-dipropoxycalix[4]arene (1031858-84-0)

Conditions	Yield
With triethylamine In dichloromethane at 20℃;	24%

diazomethane (186581-53-3, 908094-01-9) + N-acetylleucine (99-15-0) → methyl N-acetyl-leucinate (57289-25-5)

Conditions	Yield
With diethyl ether; ethanol l(-)-acetylleucine methyl ester;
In diethyl ether
In methanol; diethyl ether at 10℃; Yield given;

ethanol (64-17-5) + N-acetylleucine (99-15-0) → ethyl N-acetyl-leucinate (4071-36-7)

N-acetylleucine (99-15-0) → N-Ac-Leu (1188-21-2)

Conditions	Yield
With (-)-α-fenchylamine

N-acetylleucine (99-15-0) → N-acetyl-D-leucine (19764-30-8)

Conditions	Yield
With (-)-α-fenchylamine
With (S)-1-phenyl-ethylamine
mit Hilfe eines Enzym-Praepaprats aus Aspergillus oder Penicillium;
mit Hilfe eines Enzym-Praepaprats aus Schweine-Nieren;

N-acetylleucine (99-15-0) + chloroformic acid ethyl ester (541-41-3) → N-<2-(1-hydroxy-4-methylpentyl)>acetamide (150206-13-6)

Conditions	Yield
With tetrahydrofuran; 1-ethyl-piperidine beim Erwaermen der Reaktionsloesung mit Lithiumboranat;

N-acetylleucine (99-15-0) + aniline (62-53-3) → N-acetyl-L-leucine anilide (68200-02-2)

Conditions	Yield
With papain

N-acetylleucine (99-15-0) + [bis(acetoxy)iodo]benzene (3240-34-4) → (Di-N-acetyl-D,L-leucyloxyjod)-benzol

Conditions	Yield
In chlorobenzene under 25 - 35 Torr;

Upstream product

• 108-24-7 acetic anhydride 
• 328-39-2 LEUCINE 
• 60-35-5 acetamide 
• 201230-82-2 carbon monoxide 
• 556-82-1 3-methyl-2-buten-1-ol 
• 105746-99-4 3,10-diethyl-3,6,10-trimethyl-4,9-dioxa-3,10-disiladodecane 
• 1188-21-2 N-Ac-Leu 
• 76-05-1 trifluoroacetic acid 
• 7732-18-5 water 
• 75-36-5 acetyl chloride 
• 830-03-5 4-nitrophenol acetate 
• 37944-29-9 ethyl 2-acetamido-2-ethoxycarbonyl-4-methyl-4-pentenoic acid 
• 151962-48-0 acetylamino-isobutyl-malonic acid diethyl ester 
• 5429-56-1 N-Acetamidoacrylic acid 

Downstream Products

• 61-90-5 L-leucine 
• 1188-21-2 N-Ac-Leu 
• 150577-30-3 3-Acetyl-4-isobutyl-5-oxazolidinone 
• 19764-30-8 N-acetyl-D-leucine 
• 64-19-7 acetic acid 
• 328-39-2 LEUCINE 
• 10303-64-7 2-hydroxy-4-methylpentanoic acid 
• 251988-76-8 N-[3-methyl-1-(4-methyl-benzoyl)-butyl]-acetamide 
• 68200-02-2 N-acetyl-L-leucine anilide 
• 4071-36-7 ethyl N-acetyl-leucinate 
• 1462-78-8 2-Acetamino-isocapronsaeure- 

Relevant articles and documents

Minisci-Type Alkylation of N-Heteroarenes by N-(Acyloxy)phthalimide Esters Mediated by a Hantzsch Ester and Blue LED Light

A synthetic method that enables the Hantzsch ester-mediated Minisci-type C2-alkylation of quinolines, isoquinolines and pyridines by N-(acyloxy)phthalimide esters (NHPI) under blue LED (light emitting diode) light (456 nm) is described. Achieved under mild reaction conditions at room temperature, the metal-free synthetic protocol was shown to be applicable to primary, secondary and tertiary NHPIs to give the alkylated N-heterocyclic products in yields of 21–99%. On introducing a chiral phosphoric acid, an asymmetric version of the reaction was also realised and provided product enantiomeric excess (ee) values of 53–99%. The reaction mechanism was delineated to involve excitation of an electron-donor acceptor (EDA) complex, formed from weak electrostatic interactions between the Hantzsch ester and NHPI, which generates the posited radical species of the redox active ester that undergoes addition to the N-heterocycle.

Regioselective synthesis of tetrasubstituted pyrroles by 1,3-dipolar cycloaddition and spontaneous decarboxylation

We developed a novel regioselective synthesis of tetrasubstituted pyrroles via the classic 1,3-dipolar cycloaddition of α,β-unsaturated benzofuran-3(2H)-one and azlactones (1) followed by spontaneous decarboxylation. The complete regiochemical control of tetrasubstituted pyrroles was confirmed by the orthogonal synthesis of complementary regioisomers (7a and 7b) simply by using different azlactones (1a and 1b, respectively).

METHOD OF AMIDOCARBONYLATION REACTION

A novel method of an amidocarbonylation reaction among an aldehyde compound, an amide compound, and carbon monoxide, which comprises using a palladium-supporting crosslinked-polymer composition containing palladium clusters having a major-axis length of 20 nm or shorter to conduct the amidocarbonylation reaction. Thus, an N-acyl-±-amino acid can be more efficiently and selectively synthesized in a clean reaction system. Also provided is a catalyst for use in the method.