1078-21-3

Basic information

• Product Name: 4-Amino-3-phenylbutanoic acid
• Synonyms: TIMTEC-BB SBB001567;PHENIBUT;4-amino-3-phenylbutanoicacid;4-amino-3-phenyl-butyricaci;beta-(aminomethyl)-benzenepropanoicaci;beta-(aminomethyl)benzenepropanoicacid;beta-(aminomethyl)hydrocinnamicacid;beta-phenyl-gamma-aminobutyrate
• CAS NO: 1078-21-3
• Molecular Formula: C₁₀H₁₃NO₂
• Molecular Weight: 179.2
• EINECS: 214-079-6
• Product Categories: Organic acids;Nutritions & Sterides;API;Inhibitors
• Mol File: 1078-21-3.mol
• Article Data: 18

Chemical Properties

• Melting Point: 252.5°C (rough estimate)
• Boiling Point: 311.75°C (rough estimate)
• Flash Point: 152.1 °C
• Appearance: white to off-white crystalline powder
• Density: 1.1248 (rough estimate)
• Vapor Pressure: 7.98E-05mmHg at 25°C
• Refractive Index: 1.5710 (estimate)
• Solubility: Free base: 35 mg/mL in DMSO (195.29 mM) at 25 °C (SellekChem, 2019).Hydrochloride salt (Cayman, 2016): 25 mg/ml in DMF; 20 mg/ml in DMSO; 14 mg/ml in ethanol; 10 mg/mL in PBS (pH 7.2).
• PKA: 4.10±0.10(Predicted)
• CAS DataBase Reference: 4-Amino-3-phenylbutanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Amino-3-phenylbutanoic acid(1078-21-3)
• EPA Substance Registry System: 4-Amino-3-phenylbutanoic acid(1078-21-3)

Safety Data

• Hazard Codes: Xi
• HazardClass: IRRITANT
• Hazardous Substances Data: 1078-21-3(Hazardous Substances Data)

Usage

Description

Phenibut, also known as fenibut, phenigamma, and beta-phenyl-gamma-aminobutyric acid, is a derivative of the neurotransmitter GABA. It was developed in Russia,and there it has been used clinically since the 1960s to treat anxiety and related conditions，including insomnia(Lapin，2001). Phenibut has anxiolytic properties and is commonlycompared to benzodiazepines and baclofen.Structurally，phenibut issimilar to GABA, with the addition of the phenyl ring. This allows thecompound to more easily cross the blood-brain barrier, but also changesits activity profile (Shulgina,1986). Scientific studies demonstrate that phenibut can be safely used to treat anxiety, depression,epilepsy, speech disorders, and insomnia.

Uses

4-amino-3-phenylbutanoic acid (cas# 1078-21-3) is a GABAA receptor agonist, used for treatment of disorders influenced by dysfunction of pancreatic β cells and also used in combination with other agents.

Preparation

Phenibut was synthesized by Perekalin and his associates at the Department of Organic Chemistry of the Herzen Pedagogic Institute in St. Petersburg, the Russian Federation. In initial publications phenibut was known as phenigamma (Lapin, 2001, V. V. Perekalin, 1954).Fenibut synthesis: from benzoyl chloride and ethyl acetoacetate as raw materials, through condensation and hydrolysis of ethyl benzoyl acetate, and then condensation of benzaldehyde and nitromethane to generate trans-nitrostyrene, and then the two are combined. Micheal addition, the adduct is then catalytically hydrogenated with Raney nickel, and finally hydrolyzed in concentrated hydrochloric acid to produce phenibate.Synthesis of Phenibut (16) and Baclofen (17).

Application

Phenibut is an anxiolytic and nootropic drug, discovered in the Soviet Union used to treat several psychiatric disorders. It can be used in the treatment of anxiety, depression, asthenia, post-traumatic stress disorder, stuttering, and vestibular disorders.

Safety Profile

Moderately toxic by intraperitoneal route. Human systemic effects by ingestion: somnolence, hallucinations, distorted perception. Used as a mood elevator and tranquilizer. When heated to decomposition it emits toxic fumes of NOx.

Regulatory Status

USA - Phenibut is still an uncontrolled substance in the United States, and it is legal to sell and possess phenibut. It has not been approved for clinical use in the United States. Europe - Unscheduled. It is not regulated by the European Medicines Agency. However, some nootropic substances such as piracetam are available only on prescription in some European Union countries and are freely available in others. Russia - Phenibut is a licensed prescription medication used for a variety of conditions including anxiety, insomnia, post-traumatic stress disorders, depression, stuttering, tics, attention deficit disorders, and vestibular disorders. Russian cosmonauts were reported to have been supplied with the substance to help relieve tension, anxiety and fear (Buckley 2006).

InChI:InChI=1/C10H13NO2.ClH/c11-7-9(6-10(12)13)8-4-2-1-3-5-8;/h1-5,9H,6-7,11H2,(H,12,13);1H

Synthetic route

4-nitro-3-phenylbutanoic acid (41441-41-2) → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 60℃; under 45004.5 Torr;	98%

4-(1,3-dioxoisoindolin-2-yl)-3-phenyl-N-(quinolin-8-yl)butanamide → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
With hydrogenchloride In water at 130℃; for 24h; Sealed tube;	95%

2-oxo-4-phenyl-3-ethoxycarbonylpyrrolidine (52450-32-5) → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
With hydrogenchloride

4-phenylpyrrolidin-2-one → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
With hydrogenchloride Heating;

3-cyano-3-phenyl propionic acid (14387-18-9) → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
With hydrogen; palladium on activated charcoal In acetic acid under 15200 Torr;

(+-)-3-phenyl-glutaramic acid → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
With sodium hydroxide; sodium hypobromide

hydrogenchloride (7647-01-0) + 3-phenyl-glutaric acid dihydrazide (72976-16-0) + isopentyl nitrite (110-46-3) + 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
at 25℃; Kochen mit Bromwasserstoffsaeure;

benzyl alcohol → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium hypochlorite; potassium bromide / water; dichloromethane / 0.21 h / 0 °C 2.1: potassium tert-butylate / toluene; methanol / 0.17 h / 20 °C / 4500.45 Torr / Inert atmosphere 2.2: 0.11 h / 25 °C / 4500.45 Torr / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / toluene; tetrahydrofuran / 1 h / 50 °C / 6000.6 Torr 4.1: lithium hydroxide; water / toluene / 1 h / 50 °C / 3750.38 Torr 5.1: hydrogen; palladium 10% on activated carbon / methanol / 60 °C / 45004.5 Torr View Scheme

benzaldehyde (100-52-7) → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: potassium tert-butylate / toluene; methanol / 0.17 h / 20 °C / 4500.45 Torr / Inert atmosphere 1.2: 0.11 h / 25 °C / 4500.45 Torr / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / toluene; tetrahydrofuran / 1 h / 50 °C / 6000.6 Torr 3.1: lithium hydroxide; water / toluene / 1 h / 50 °C / 3750.38 Torr 4.1: hydrogen; palladium 10% on activated carbon / methanol / 60 °C / 45004.5 Torr View Scheme

methyl cinnamate (103-26-4) → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrabutyl ammonium fluoride / toluene; tetrahydrofuran / 1 h / 50 °C / 6000.6 Torr 2: lithium hydroxide; water / toluene / 1 h / 50 °C / 3750.38 Torr 3: hydrogen; palladium 10% on activated carbon / methanol / 60 °C / 45004.5 Torr View Scheme

4-nitro-3-phenylbutanoic acid methyl ester (34687-03-1) → 4-amino-3-phenylbutanoic acid (1078-21-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: lithium hydroxide; water / toluene / 1 h / 50 °C / 3750.38 Torr 2: hydrogen; palladium 10% on activated carbon / methanol / 60 °C / 45004.5 Torr View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) + 2-Fluorobenzaldehyde (446-52-6) + methyl 2,4-dioxopentanoate (20577-61-1) → 4-[3-acetyl-2-(2-fluoro-phenyl)-4-hydroxy-5-oxo-2,5-dihydro-pyrrol-1-yl]-3-phenyl-butyric acid

Conditions	Yield
In ethanol; water at 20℃; for 12h; Condensation;	78%

di-tert-butyl dicarbonate (24424-99-5) + 4-amino-3-phenylbutanoic acid (1078-21-3) → 4-((tert-butoxycarbonyl)amino)-3-phenylbutanoic acid (189014-01-5)

Conditions	Yield
With sodium hydroxide In water; tert-butyl alcohol at 0 - 20℃;	73%

4-amino-3-phenylbutanoic acid (1078-21-3) + benzyl alcohol (100-51-6) → C17H19NO2*(x)ClH

Conditions	Yield
With thionyl chloride at 0 - 20℃; for 16h;	66%

4-amino-3-phenylbutanoic acid (1078-21-3) + N,N'-diisopropyl-O-methylisourea (54648-79-2) → C13H19NO2 (129453-46-9)

Conditions	Yield
In methanol for 120h; Ambient temperature;	65%

phthalic anhydride (85-44-9) + 4-amino-3-phenylbutanoic acid (1078-21-3) → 4-(1,3-dioxoisoindolin-2-yl)-3-phenylbutanoic acid

Conditions	Yield
In ethanol for 3h; Reflux;	62%

4-amino-3-phenylbutanoic acid (1078-21-3) → 4-phenylpyrrolidin-2-one (1198-97-6)

Conditions	Yield
With potassium hydroxide

4-amino-3-phenylbutanoic acid (1078-21-3) → (RS)-2-(2-oxo-4-phenylpyrrolidin-1-yl)acetamide (77472-70-9)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium hydroxide / ethanol / 65 - 75 °C 2: ethanol / 65 - 75 °C 3: acetic acid / ethanol 4: Heating View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → 4-[(2-amino-2-oxoethyl)amino]-3-phenylbutanoic acid

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydroxide / ethanol / 65 - 75 °C 2: ethanol / 65 - 75 °C 3: acetic acid / ethanol View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → 4-[bis(2-amino-2-oxoethyl)amino]-3-phenylbutanoic acid sodium salt

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium hydroxide / ethanol / 65 - 75 °C 2: ethanol / 65 - 75 °C 3: acetic acid / ethanol 4: sodium hydroxide / ethanol / 65 - 75 °C 5: ethanol / 65 - 75 °C View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → C10H12NO2(1-)*K(1+)

Conditions	Yield
With potassium hydroxide In ethanol at 65 - 75℃;

4-amino-3-phenylbutanoic acid (1078-21-3) → C12H15N2O3(1-)*K(1+)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium hydroxide / ethanol / 65 - 75 °C 2: ethanol / 65 - 75 °C View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → C12H15N2O3(1-)*Na(1+)

Conditions	Yield
Multi-step reaction with 4 steps 1: potassium hydroxide / ethanol / 65 - 75 °C 2: ethanol / 65 - 75 °C 3: acetic acid / ethanol 4: sodium hydroxide / ethanol / 65 - 75 °C View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → N-(4-hydroxy-2-phenylbutyl)-2H-benzo[e][1,2,4]thiadiazine-3-carboxamide 1,1-dioxide

Conditions

Yield

Multi-step reaction with 6 steps 1.1: sodium hydroxide / water; tert-butyl alcohol / 0 - 20 °C 2.1: potassium carbonate / tetrahydrofuran / 0.25 h / 20 °C 2.2: 20 °C 3.1: hydrogenchloride / ethyl acetate / 3 h / 20 °C 4.1: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 20 °C 5.1: sodium hydroxide / 3 h / 20 °C 6.1: borane-THF / tetrahydrofuran / 3 h / 20 °C / Inert atmosphere View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → tert-butyl (3-amino-2-phenylpropyl)carbamate (437708-57-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: ethanol / 3 h / Reflux 2: triethylamine; diphenyl phosphoryl azide / 1,4-dioxane / 100 °C 3: hydrazine hydrate / ethanol / 2 h / 80 °C View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → tert-butyl (3-(1,1-dioxido-2H-benzo[e][1,2,4]thiadiazine-3-carboxamido)-2-phenylpropyl)carbamate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: ethanol / 3 h / Reflux 2.1: triethylamine; diphenyl phosphoryl azide / 1,4-dioxane / 100 °C 3.1: hydrazine hydrate / ethanol / 2 h / 80 °C 4.1: sodium hydrogencarbonate / dichloromethane / 0.17 h / 20 °C 4.2: 1 h / 20 °C View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → N-(3-amino-2-phenylpropyl)-2H-benzo[e][1,2,4]thiadiazine-3-carboxamide 1,1-dioxide hydrochloride

Conditions	Yield
Multi-step reaction with 5 steps 1.1: ethanol / 3 h / Reflux 2.1: triethylamine; diphenyl phosphoryl azide / 1,4-dioxane / 100 °C 3.1: hydrazine hydrate / ethanol / 2 h / 80 °C 4.1: sodium hydrogencarbonate / dichloromethane / 0.17 h / 20 °C 4.2: 1 h / 20 °C 5.1: hydrogenchloride / ethyl acetate / 2 h / 20 °C View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → methyl 4-amino-3-phenylbutanoate hydrochloride (25271-46-9)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium hydroxide / water; tert-butyl alcohol / 0 - 20 °C 2.1: potassium carbonate / tetrahydrofuran / 0.25 h / 20 °C 2.2: 20 °C 3.1: hydrogenchloride / ethyl acetate / 3 h / 20 °C View Scheme

4-amino-3-phenylbutanoic acid (1078-21-3) → methyl 4-(1,1-dioxido-2H-benzo[e][1,2,4]thiadiazine-3-carboxamido)-3-phenylbutanoate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium hydroxide / water; tert-butyl alcohol / 0 - 20 °C 2.1: potassium carbonate / tetrahydrofuran / 0.25 h / 20 °C 2.2: 20 °C 3.1: hydrogenchloride / ethyl acetate / 3 h / 20 °C 4.1: triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / dichloromethane / 20 °C View Scheme

Upstream product

• 1078203-19-6 D-gaMMa-glu(oMe)-lys(tfa)-d-ala-d-ala-oMe 
• 107819-90-9 1,3-DI-BOC-2-METHYLISOTHIOUREA 
• 1078-19-9 6-Methoxytetralone 
• 107819-11-4 N~1~-dodecylpropane-1,2-diamine 
• 107819-09-0 1-phenoxy-2-(trichloromethoxy)benzene 
• 107819-08-9 1,2,3,4-tetrachloro-5-methoxy-6-phenoxybenzene 
• 107819-07-8 1-(dichloromethoxy)dibenzo[b,d]furan 
• 107819-06-7 1,2,3,4-tetrachloro-5-(2,3-dichlorophenoxy)-6-methoxybenzene 
• 107818-55-3 3-Amino-5-bromo-thiophene-2-carboxylic acid methyl ester 
• 107818-51-9 methyl 3-amino-5-chlorothiophene-2-carboxylate 
• 107818-20-2 THIENO(3 2-B)PYRIDIN-7-OL 
• 107817-86-7 1-(4-chlorobenzyl)-4-[(2E)-3-(2,4-dichlorophenyl)prop-2-en-1-yl]piperazine dihydrochloride 
• 1078-17-7 3-PHENYL-DL-SERINE 
• 107817-60-7 tricrozarin A 

Downstream Products

• 107821-65-8 2-(anilinomethyl)-4-nitro-1H-isoindole-1,3(2H)-dione 
• 107-82-4 1-Bromo-3-methylbutane 
• 107824-41-9 poly(d(Tm(5)C)).poly(d(GA)).poly(d(m(5)CT)) 
• 107824-63-5 NCO I 
• 107825-27-4 Ethanethione, 2-(4-fluorophenyl)-1-(4-Morpholinyl)- 
• 107826-16-4 obelmycin F 
• 107826-17-5 obelmycin E 
• 107827-75-8 phosphorane, dimethyl(2-methylundecyl)-, oxide 
• 107827-77-0 5-Dodecanoylaminofluorescein 
• 1078-27-9 7-methoxy-1,2,3,4-tetrahydroisoquinolin-6-ol 
• 1078-28-0 6-Methoxyquinaldine 
• 107828-11-5 5-(propan-2-yloxy)-1,3-benzodioxole 
• 107829-09-4 N-(3-nitrophenyl)butanamide 
• 107829-39-0 4-tert-butyl-1-(4-ethynylphenyl)-2,6,7-trioxabicyclo[2.2.2]octane-3-carbonitrile 

Recommend Products

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• 7647-01-0  hydrogenchloride 
• 72976-16-0  3-phenyl-glutaric acid dihydrazide 
• 110-46-3  isopentyl nitrite 
• 1078-21-3  (R)-Phenibut 
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