10009-20-8

Basic information

• Product Name: N-6-Trifluoroacetyl-L-lysine
• Synonyms: H-LYS(TFA)-OH;H-LYS(CF3CO)-OH;EPSILON-TFA-LYSINE;LYSINE(TFA)-OH;N-EPSILON-TRIFLUOROACETYL-L-LYSINE;N6-TRIFLUOROACETYL-L-LYSINE;N-ε-Trifluoroacetyl-L-lysine;N1-Trifluoroacetyl-L-Lysine
• CAS NO: 10009-20-8
• Molecular Formula: C₈H₁₃F₃N₂O₃
• Molecular Weight: 242.2
• EINECS: 1308068-626-2
• Product Categories: Chemical intermediate for LISINOPRIL;API intermediates;Amino Acids & Derivatives;Metabolites & Impurities;amino acid;Amino Acids & Derivatives, Metabolites & Impurities
• Mol File: 10009-20-8.mol
• Article Data: 4

Chemical Properties

• Melting Point: 258
• Boiling Point: 382.5 °C at 760 mmHg
• Flash Point: 185.1 °C
• Appearance: /
• Density: 1.4
• Vapor Pressure: 6.55E-07mmHg at 25°C
• Refractive Index: 1.444
• Storage Temp.: 2-8°C
• Solubility: 2 M HCl: 10 mg/mL, clear, colorless
• PKA: 2.51±0.24(Predicted)
• BRN: 2122429
• CAS DataBase Reference: N-6-Trifluoroacetyl-L-lysine(CAS DataBase Reference)
• NIST Chemistry Reference: N-6-Trifluoroacetyl-L-lysine(10009-20-8)
• EPA Substance Registry System: N-6-Trifluoroacetyl-L-lysine(10009-20-8)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 1
• F: 10
• Hazardous Substances Data: 10009-20-8(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Uses

A cysteine conjugate metabolite adduct formation with specific mitochondrial proteins using antibodies raised against halothane metabolite adducts.

Definition

ChEBI: An N6-acyl-L-lysine where the N6-acyl group is trifluoroacetyl.

InChI:InChI=1/C8H13F3N2O3/c9-8(10,11)7(16)13-4-2-1-3-5(12)6(14)15/h5H,1-4,12H2,(H,13,16)(H,14,15)/t5-/m0/s1

Synthetic route

ethyl trifluoroacetate, (383-63-1) + L-Lysine hydrochloride (657-27-2, 10098-89-2) → (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8)

Conditions	Yield
With sodium In ethanol at 5 - 20℃;	62%
Stage #1: L-Lysine hydrochloride With ethanol; sodium Stage #2: ethyl trifluoroacetate, In ethanol at 20℃; Cooling with ice; Stage #3: With acetic acid In ethanol	62%
Stage #1: L-Lysine hydrochloride With sodium In ethanol for 1h; Stage #2: ethyl trifluoroacetate, at 5 - 20℃; for 3h; Stage #3: With acetic acid for 0.166667h;	56%

ethyl trifluoroacetate, (383-63-1) + sodium salt of L-lysine (16079-52-0) → (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + Nα,Nε-bis(trifluoroacetyl)-L-lysine (329-53-3)

Conditions	Yield
In ethanol at 5 - 20℃;	A 25% B 56%

S-ethyl trifluoroacetate (383-64-2) + L-Lysine hydrochloride (657-27-2, 10098-89-2) → (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8)

Conditions	Yield
With sodium hydroxide

di-tert-butyl dicarbonate (24424-99-5) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → (S)-6-trifluoroacetylamino-2-(tert-butoxycarbonylamino)-hexanoic acid (96561-04-5, 16965-06-3)

Conditions	Yield
Stage #1: di-tert-butyl dicarbonate; (S)-6-trifluoroacetylamino-2-aminohexanoic acid With triethylamine In N,N-dimethyl-formamide at 20℃; for 3h; Stage #2: With hydrogenchloride In water; N,N-dimethyl-formamide pH=2;	92%
In N,N-dimethyl-formamide at 20℃; for 2h;	92%

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + N-phenyl-1H-benzo[d][1,2,3]triazole-1-carboxamide (86298-24-0) → C15H18F3N3O4

Conditions	Yield
With triethylamine In water; acetonitrile at 20℃; for 0.5h; chemoselective reaction;	92%

phosgene (75-44-5) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nε-trifluoroacetyl-L-lysine Nα-carboxanhydride (42267-27-6)

Conditions	Yield
In tetrahydrofuran at 20 - 30℃; for 4.33333h; Inert atmosphere;	86.5%
In 1,4-dioxane at 45℃; for 2h;	70%

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + 1,1'-carbonyldiimidazole (530-62-1) → N-(4-(2,5-dioxo-4-oxazolidinyl)butyl)-2,2,2-trifluoroacetamide

Conditions	Yield
In tetrahydrofuran for 0.4h; Reflux; Large scale;	81.9%

bis(trichloromethyl) carbonate (32315-10-9) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nε-trifluoroacetyl-L-lysine Nα-carboxanhydride (42267-27-6)

Conditions	Yield
With sodium hydroxide In tetrahydrofuran at 50℃; Inert atmosphere;	75%
With Pinene In ethyl acetate at 105 - 110℃;

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + trichloromethyl chloroformate (503-38-8) → Nε-trifluoroacetyl-L-lysine Nα-carboxanhydride (42267-27-6)

Conditions	Yield
In tetrahydrofuran for 2h; Inert atmosphere; Reflux;	75%
With sodium hydroxide In tetrahydrofuran for 2h; Inert atmosphere; Reflux;	75%
In ethyl acetate at 70℃; for 4h;	63%

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + triethylamine (121-44-8) + mono-4-methoxytrityl chloride (14470-28-1) → C6H15N*C28H29F3N2O4

Conditions	Yield
Stage #1: (S)-6-trifluoroacetylamino-2-aminohexanoic acid With chloro-trimethyl-silane; triethylamine In dichloromethane for 2h; Reflux; Inert atmosphere; Stage #2: mono-4-methoxytrityl chloride In dichloromethane for 2h; Reflux; Inert atmosphere; Stage #3: triethylamine In methanol; dichloromethane for 0.5h; Inert atmosphere;	74%

potassium cyanate (590-28-3) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nα-carbamoyl-Nε-trifluoroacetyl-L-lysine

Conditions	Yield
In water at 50℃; for 3h; pH=7.5;	73.8%
In water at 50℃; pH=8; Kinetics;

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + docosa-10,12-diynedioic acid mono-(2,5-dioxo-pyrrolidin-1-yl) ester (340701-06-6) → 21-[(S)-1-Carboxy-5-(2,2,2-trifluoro-acetylamino)-pentylcarbamoyl]-henicosa-10,12-diynoic acid

Conditions	Yield
With potassium hydroxide In tetrahydrofuran at 20℃; for 24h; pH=9;	62%

methanol (67-56-1) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → methyl 2-bromo-6-(2,2,2-trifluoroacetamido)hexanoate

Conditions	Yield
Stage #1: (S)-6-trifluoroacetylamino-2-aminohexanoic acid With sulfuric acid; hydrogen bromide; sodium bromide; sodium nitrite In water at 3 - 20℃; Inert atmosphere; Stage #2: methanol With toluene-4-sulfonic acid at 65℃; Inert atmosphere;	62%

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → C16H22F6N4O4 (366001-61-8)

Conditions	Yield
phosphorus pentoxide In 1-methyl-pyrrolidin-2-one at 170℃; Product distribution / selectivity;	59%

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + benzyl chloroformate (501-53-1) → (2S)-2-{[(benzyloxy)carbonyl]amino}-6-[(trifluoroacetyl)amino]hexanoic acid (14905-30-7)

Conditions	Yield
With sodium hydrogencarbonate

phosgene (75-44-5) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nε-trifluoroacetyl-L-lysine Nα-carboxanhydride (42267-27-6) + C9H11Cl2F3N2O3 (112139-30-7)

Conditions	Yield
In tetrahydrofuran; N,N-dimethyl-formamide at 30℃; for 2.5h; Title compound not separated from byproducts;

phosgene (75-44-5) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → C9H12ClF3N2O4 (112139-31-8)

Conditions	Yield
In tetrahydrofuran at 30℃; for 2.5h;

chloro-trimethyl-silane (75-77-4) + (S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → C11H21F3N2O3Si (110579-79-8)

Conditions	Yield
In chloroform; acetonitrile for 2h; Heating;

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + N,O-Bis(trimethylsilyl)acetamide (10416-59-8, 132255-83-5) → C14H29F3N2O3Si2

Conditions	Yield
In 1,4-dioxane

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) + 2-nitrobenzenesulfenyl chloride (7669-54-7) → Nα-(o-nitrophenylsulfenyl)-Nε-(trifluoroacetyl)lysine (41918-63-2)

Conditions	Yield
With sodium hydroxide In acetone

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → 21-((S)-5-Amino-1-carboxy-pentylcarbamoyl)-henicosa-10,12-diynoic acid (736142-36-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 62 percent / aq. KOH / tetrahydrofuran / 24 h / 20 °C / pH 9 2: 46 percent / aq. KOH / tetrahydrofuran; methanol / 12 h / 35 °C / pH 12 - 13 View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Boc-Ser-Lys(TFA)-Pro-Met-Gly(OBzl)2

Conditions	Yield
Multi-step reaction with 3 steps 1: CHCl3; acetonitrile / 2 h / Heating 2: 48 percent / pyridine, triethylamine, pivaloyl chloride / CHCl3; acetonitrile / 1 h / Ambient temperature 3: 53 percent / diphenylphosphorazide, triethylamine / dioxane; dimethylformamide / 7 h, 0 deg C; 40 h, 20 deg C View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nα-tert-butyloxycarbonyl-L-seryl-Nε-trifluoroacetyl-L-lysine (107994-57-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: CHCl3; acetonitrile / 2 h / Heating 2: 48 percent / pyridine, triethylamine, pivaloyl chloride / CHCl3; acetonitrile / 1 h / Ambient temperature View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nα-(o-nitrophenylsulfenyl)-Nε-(trifluoroacetyl)-L-lysine N-hydroxysuccinimide ester (64851-79-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 2N NaOH / acetone 2: dicyclohexylcarbodiimide / dioxane; CH2Cl2 / 7 h / 0 - 20 °C View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → N-tert-butoxycarbonyl-L-leucyl-Nε-(trifluoroacetyl)-L-lysyl-L-leucine methyl ester (82175-93-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 2N NaOH / acetone 2: dicyclohexylcarbodiimide / dioxane; CH2Cl2 / 7 h / 0 - 20 °C 3: 1.) triethylamine / 1.) dioxane, methylene chloride, 15 min, 2.) 0 - 20 deg C, 7 h 4: HCl / ethyl acetate; diethyl ether / 0.33 h / 20 °C 5: 69.5 percent / triethylamine / dioxane; CH2Cl2 / 16 h / 0 - 20 °C View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nα-(o-nitrophenylsulfenyl)-Nε-(trifluoroacetyl)-L-lysyl-L-leucine methyl ester (82175-92-6)

Conditions	Yield
Multi-step reaction with 3 steps 1: 2N NaOH / acetone 2: dicyclohexylcarbodiimide / dioxane; CH2Cl2 / 7 h / 0 - 20 °C 3: 1.) triethylamine / 1.) dioxane, methylene chloride, 15 min, 2.) 0 - 20 deg C, 7 h View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nε-(trifluoroacetyl)-L-lysyl-L-leucine methyl ester hydrochloride

Conditions	Yield
Multi-step reaction with 4 steps 1: 2N NaOH / acetone 2: dicyclohexylcarbodiimide / dioxane; CH2Cl2 / 7 h / 0 - 20 °C 3: 1.) triethylamine / 1.) dioxane, methylene chloride, 15 min, 2.) 0 - 20 deg C, 7 h 4: HCl / ethyl acetate; diethyl ether / 0.33 h / 20 °C View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nα-(o-nitrophenylsulfenyl)-Nε-(trifluoroacetyl)-L-lysyl-L-alanyl-L-alanine methyl ester (82175-94-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 2N NaOH / acetone 2: dicyclohexylcarbodiimide / dioxane; CH2Cl2 / 7 h / 0 - 20 °C 3: 50.9 percent / triethylamine / dioxane; CH2Cl2 / 16 h / 0 - 20 °C View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nε-trifluoroacetyl-L-lysine Nα-carboxanhydride (42267-27-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran / 2.5 h / 30 °C 2: 88 percent / tetrahydrofuran / 4 h / 25 °C View Scheme

(S)-6-trifluoroacetylamino-2-aminohexanoic acid (10009-20-8) → Nε-(trifluoroacetyl)-L-lysyl-L-proline (103300-89-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrahydrofuran; dimethylformamide / 2.5 h / 30 °C 2: 94 percent Chromat. / tetrahydrofuran; H2O / 0.03 h / 0 - 12 °C View Scheme
Multi-step reaction with 3 steps 1: tetrahydrofuran / 2.5 h / 30 °C 2: 88 percent / tetrahydrofuran / 4 h / 25 °C 3: 94 percent Chromat. / tetrahydrofuran; H2O / 0.03 h / 0 - 12 °C View Scheme

Upstream product

• 383-63-1 ethyl trifluoroacetate, 
• 16079-52-0 sodium salt of L-lysine 
• 657-27-2 L-Lysine hydrochloride 
• 383-64-2 S-ethyl trifluoroacetate 

Downstream Products

• 42267-27-6 N^ε-trifluoroacetyl-L-lysine N^α-carboxanhydride 
• 199002-02-3 N₂-[1-(S)-ethoxycarbonyl-3-oxo-3-phenylpropyl]-N₆-trifluoroacetyl-L-lysine 
• 96561-04-5 (S)-6-trifluoroacetylamino-2-(tert-butoxycarbonylamino)-hexanoic acid 
• 14905-34-1 TFA-Lys(Z)-Gly-OBu-t 
• 14905-35-2 TFA-Lys(Z)-Gly 
• 103300-89-6 N^ε-(trifluoroacetyl)-L-lysyl-L-proline 
• 82175-94-8 N^α-(o-nitrophenylsulfenyl)-N^ε-(trifluoroacetyl)-L-lysyl-L-alanyl-L-alanine methyl ester 
• 82175-92-6 N^α-(o-nitrophenylsulfenyl)-N^ε-(trifluoroacetyl)-L-lysyl-L-leucine methyl ester 
• 64851-79-2 N^α-(o-nitrophenylsulfenyl)-N^ε-(trifluoroacetyl)-L-lysine N-hydroxysuccinimide ester 
• 41918-63-2 N^α-(o-nitrophenylsulfenyl)-N^ε-(trifluoroacetyl)lysine 
• 112139-30-7 C₉H₁₁Cl₂F₃N₂O₃ 
• 14905-30-7 (2S)-2-{[(benzyloxy)carbonyl]amino}-6-[(trifluoroacetyl)amino]hexanoic acid 

Relevant articles and documents

N-trifluoroacyl lysine derivatives in the synthesis of L-lysyl-L-glutamic acid

Conditions were developed for simultaneous preparation of N a-trifluoroacetyl-L-lysine and N α,N a-bis(trifluoroacetyl)-L-lysine at overall conversion of initial lysine monohydrochloride up to 82%. By reaction of dimethyl L-glutamate with N α,N a-bis(trifluoroacetyl)-L-lysyl chloride in the presence of triethylamine or with N α- carboxyanhydride of N a-trifluoroacetyl-L-lysine with subsequent removing protecting groups in the formed dipeptides by treating with water-ethanol solution of sodium hydroxide we obtained L-lysyl-L-glutamic acid. Physicochemical characteristics of samples obtained coincided with characteristics of L-lysyl-L-glutamic acid described in the literature thus suggesting that no racemization occurred either at the stage of peptide bond formation or at deprotection.

THERAPIES FOR CANCER USING ISOTOPICALLY SUBSTITUTED LYSINE

Methods of treatment and substances for treatment of cancer may use or cause the creation of isotopically modified lysine at levels that do not occur naturally.