7013-05-0

Basic information

• Product Name: (S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID
• Synonyms: (S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID;(S)-4-AMINO-3-HYDROXYBUTANOIC ACID;(S)-4-AMINO-3-HYDROXYBUTYRIC ACID;(S)-(+)-AMINO-3-HYDROXYBUTANOIC ACID;BUTANOIC ACID, 4-AMINO-3-HYDROXY-, (S);(3S)-(+)-4-Amino-3-hydroxybutanoic acid;(3S)-4-Amino-3-hydroxybutanoic acid;(S)-(+)-3-Hydroxy-GABA
• CAS NO: 7013-05-0
• Molecular Formula: C₄H₉NO₃
• Molecular Weight: 119.12
• Product Categories: chiral;Carboxylic Acids;Chiral Building Blocks;Organic Building Blocks
• Mol File: 7013-05-0.mol
• Article Data: 23

Chemical Properties

• Melting Point: 207-212 °C
• Boiling Point: 374.5 °C at 760 mmHg
• Flash Point: 180.3 °C
• Appearance: white to light yellow crystal powder
• Density: 1.312 g/cm³
• Vapor Pressure: 3.84E-07mmHg at 25°C
• Refractive Index: 1.51
• Storage Temp.: Keep in dark place,Inert atmosphere,Room temperature
• PKA: 4.04±0.10(Predicted)
• CAS DataBase Reference: (S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID(7013-05-0)
• EPA Substance Registry System: (S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID(7013-05-0)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 7013-05-0(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystal powde

Uses

S-(+)-GABOB anticonvulsant and is used in the treatment of epilepsy as it binds to the GABAB receptor.

General Description

(S)-(+)-4-Amino-3-hydroxybutyric acid [(S)-GABOB] can be prepared starting from ethyl (S)-4-chloro-3-hydroxybutyrate.

InChI:InChI=1/C4H9NO3/c5-2-3(6)1-4(7)8/h3,6H,1-2,5H2,(H,7,8)/t3-/m0/s1

Synthetic route

(-)-ethyl 3-cyano-3-hydroxypropionate (132882-98-5) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With borane-THF; nickel dichloride In isopropyl alcohol for 2h; Ambient temperature;	100%

(S)-4-Amino-3-hydroxy-butyric acid ethyl ester → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogenchloride for 1h;	100%

(S)-3-tert-Butoxy-4-tert-butoxycarbonylamino-butyric acid (99475-69-1) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogenchloride In 1,4-dioxane for 16h; Ambient temperature;	95%

(2S,5R,6S)-2-(4-benzyloxycarbonyl-5,6-diphenyl-1,2,5,6-tetrahydro-4H-1,4-oxazin-2-yl)acetic acid (213687-65-1) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogen; palladium dichloride In tetrahydrofuran; water at 75 - 80℃; under 6205.78 Torr; for 3h;	93%
With carboxylic acid; lithium; tert-butyl alcohol In tetrahydrofuran; ammonia at -78 - -33℃; for 0.833333h; Reduction; Birch reduction;	81%

(S)-4-(benzyl-benzyloxycarbonyl-amino)-3-benzyloxy-butyric acid (1431373-89-5) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethyl acetate under 760.051 Torr; for 12h;	87%

(S)-4-chloro-3-hydroxybutanamide (175158-38-0) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
Stage #1: (S)-4-chloro-3-hydroxybutanamide With ammonium hydroxide at 20℃; for 18h; amination; Stage #2: With Amberlite IRA-120B (H+) Hydrolysis;	80%

4-<(Benzyloxycarbonyl)amino>-3-hydroxybutanoic acid (83349-20-6) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + (R)-4-Amino-3-hydroxybutanoic acid (7013-07-2)

Conditions	Yield
With hydrogen; palladium on activated charcoal In methanol; water for 0.5h; Ambient temperature;	A n/a B 79%
With hydrogen; palladium on activated charcoal In methanol; water for 0.5h; Ambient temperature;

acide (S)-benzamido-4 hydroxy-3 butanoique (111607-76-2) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogen bromide for 4h; Heating;	75%

(S)-3-(benzyloxy)-4-(benzyloxycarbonylamino)butyric acid (1607830-40-9) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 11251.1 Torr; Inert atmosphere;	73%

(S)-4-amino-3-(benzyloxy)butyric acid → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In methanol at 20℃; under 11251.1 Torr;	73%

(S)-methyl 4-(((benzyloxy)carbonyl)amino)-3-hydroxybutanoate → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogenchloride In water Reflux;	73%

(2R)-2-(tert-Butyl)-3-methoxycarbonyl-1,3-oxazolidin-5-ylessigsaeure (122697-90-9) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogenchloride for 5h; Heating;	22%

3,4 epoxybutyric acid (109462-43-3) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With ammonium hydroxide for 2h;	20 mg
With ammonia

[(5S)-2-oxo-1,3-oxazolidin-5-yl]acetic acid (851387-87-6) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogenchloride for 7h; Heating;
With hydrogenchloride at 110 - 120℃; for 7h;

(R)-(-)-4-chloro-3-hydroxybutanoic acid (95574-97-3) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + (R)-4-Amino-3-hydroxybutanoic acid (7013-07-2)

Conditions	Yield
With ammonium hydroxide for 14h; Ambient temperature; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(S)-methyl 4-amino-3-hydroxybutanoate hydrochloride → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With water for 4h; Heating; Yield given;

N-(<(2R,4S)-2-(tert-butyl)-6-oxo-1,3-dioxan-4-yl>methyl)acetamide (116332-79-7) → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogenchloride for 2.5h; Heating;	160 mg

Acetic acid (S)-1-aminomethyl-2-cyano-ethyl ester → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogenchloride for 5h; Heating; Yield given;

(S)-3-Acetoxy-4-amino-butyric acid methyl ester → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With potassium carbonate In methanol for 8h; Ambient temperature; Yield given;

d-γ-benzamino-β-oxy-butyric acid → (S)-4-amino-3-hydroxybutanoic acid (7013-05-0)

Conditions	Yield
With hydrogen bromide
With hydrogen bromide vermutlich nicht ganz rein erhalten;

formaldehyd (50-00-0) + (S)-4-amino-3-hydroxybutanoic acid (7013-05-0) → (S)-4-Dimethylamino-3-hydroxy-butyric acid (99211-78-6)

Conditions	Yield
With hydrogen; palladium on activated charcoal In water at 20℃; under 4137.18 Torr; for 36h;	99%

(S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + benzyl alcohol (100-51-6) → C11H15NO3*ClH

Conditions	Yield
With thionyl chloride at 70℃; for 2h;	95%

(S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + 1,1,1,3,3,3-hexamethyl-disilazane (999-97-3) → (S)-4-Trimethylsilanyloxy-pyrrolidin-2-one

Conditions	Yield
With chloro-trimethyl-silane In xylene for 8h; Cycloaddition; Heating;	85%

(S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + 4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2,5-difluorobenzaldehyde → (3S)-4-{[(4-{[3-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-methylphenyl]methoxy}-2,5-difluorophenyl)methyl]amino}-3-hydroxybutanoic acid hydrochloride

Conditions	Yield
With sodium cyanoborohydride; acetic acid In N,N-dimethyl-formamide at 80℃; for 3h;	36%

(S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + 5-((2-formyl-4-methyl-5-(((2-methyl-[1,1′-biphenyl]-3-yl)methyl)amino)phenoxy)methyl)nicotinonitrile → (S)-4-((2-((5-cyanopyridin-3-yl)methoxy)-5-methyl-4-(((2-methyl-[1,1′-biphenyl]-3-yl)methyl)amino)benzyl)amino)-3-hydroxybutanoic acid + (S)-5-((2-((4-hydroxy-2-oxopyrrolidin-1-yl)methyl)-4-methyl-5-(((2-methyl-[1,1′-biphenyl]-3-yl)methyl)amino)phenoxy)methyl)nicotinonitrile

Conditions	Yield
Stage #1: (S)-4-amino-3-hydroxybutanoic acid; 5-((2-formyl-4-methyl-5-(((2-methyl-[1,1′-biphenyl]-3-yl)methyl)amino)phenoxy)methyl)nicotinonitrile With acetic acid In N,N-dimethyl-formamide at 35℃; for 24h; Stage #2: With C8H14BO4(1-)*Na(1+) In N,N-dimethyl-formamide for 24h;	A 25% B 10%

methanol (67-56-1) + (S)-4-amino-3-hydroxybutanoic acid (7013-05-0) → (S)-4-amino-3-hydroxybutyric acid methyl ester (88759-60-8)

Conditions	Yield
With hydrogenchloride for 16h; Heating;
With hydrogenchloride In water at 40℃; for 3h; Temperature; Reagent/catalyst; Cooling with ice;

(S)-4-amino-3-hydroxybutanoic acid (7013-05-0) → (4S)-4-hydroxypyrrolidin-2-one (68108-18-9)

Conditions	Yield
With hydrogenchloride; 1,1,1,3,3,3-hexamethyl-disilazane 2.) iPrOH; Multistep reaction;

(S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + phenylacetyl chloride (103-80-0) → (S)-hydroxy-4 phenylacetyl-1 pyrrolidinone-2 (111607-77-3)

Conditions	Yield
With 1,1,1,3,3,3-hexamethyl-disilazane 1.) xylene, reflux, 4 h; 2.) 0 deg C to RT; Yield given. Multistep reaction;

(S)-4-amino-3-hydroxybutanoic acid (7013-05-0) + 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylic acid methyl ester (1455091-23-2) → (S)-4-(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-3-hydroxybutanoic acid (1455087-62-3)

Conditions	Yield
With sodium methylate In 2-methoxy-ethanol for 3h; Reflux;	27 mg

Upstream product

• 109462-43-3 3,4 epoxybutyric acid 
• 175158-38-0 (S)-4-chloro-3-hydroxybutanamide 
• 1607830-40-9 (S)-3-(benzyloxy)-4-(benzyloxycarbonylamino)butyric acid 
• 1431373-89-5 (S)-4-(benzyl-benzyloxycarbonyl-amino)-3-benzyloxy-butyric acid 
• 213687-65-1 (2S,5R,6S)-2-(4-benzyloxycarbonyl-5,6-diphenyl-1,2,5,6-tetrahydro-4H-1,4-oxazin-2-yl)acetic acid 
• 122697-90-9 (2R)-2-(tert-Butyl)-3-methoxycarbonyl-1,3-oxazolidin-5-ylessigsaeure 
• 99475-69-1 (S)-3-tert-Butoxy-4-tert-butoxycarbonylamino-butyric acid 
• 116332-79-7 N-(<(2R,4S)-2-(tert-butyl)-6-oxo-1,3-dioxan-4-yl>methyl)acetamide 
• 111607-76-2 acide (S)-benzamido-4 hydroxy-3 butanoique 
• 95574-97-3 (R)-(-)-4-chloro-3-hydroxybutanoic acid 
• 851387-87-6 [(5S)-2-oxo-1,3-oxazolidin-5-yl]acetic acid 
• 83349-20-6 4-<(Benzyloxycarbonyl)amino>-3-hydroxybutanoic acid 
• 132882-98-5 (-)-ethyl 3-cyano-3-hydroxypropionate 

Downstream Products

• 99211-78-6 (S)-4-Dimethylamino-3-hydroxy-butyric acid 

Relevant articles and documents

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

A family of novel chloramphenicol base-amide organocatalysts possessing a NH functionality at C-1 position as monodentate hydrogen bond donor were developed and evaluated for enantioselective organocatalytic alcoholysis of meso-cyclic anhydrides. These structural diversified organocatalysts were found to induce high enantioselectivity in alcoholysis of anhydrides and was successfully applied to the asymmetric synthesis of (S)-GABOB.

Synthesis of GABOB and GABOB-based chiral units possessing distinct protecting groups

In addition to the varied biological activity of GABOB (4-amino-3- hydroxybutanoic acid), the structure of its protected derivatives makes them interesting chiral intermediates for the synthesis of more complex compounds. A stereoselective route to GABOB derivatives with three different protecting groups is presented, using anhydride desymmetrization as a chirality-inducing step. Selective removal of the protecting groups gave compounds with a free carboxylic acid or hydroxy group. Removal of all of the protecting groups allowed GABOB to be isolated in good yield and with excellent ee. A stereoselective route to GABOB (4-amino-3-hydroxybutanoic acid) derivatives with three different protecting groups is presented. Selective deprotection produced diprotected chiral building blocks with a free carboxylic acid or hydroxy group. Removal of all the protecting groups allowed GABOB to be isolated. Copyright

Short synthesis of (R)- and (S)-4-amino-3-hydroxybutyric acid (GABOB)

A simple and stereospecific synthesis of both (R)- and (S)-GABOB has been developed. The synthetic approach involves the conversion, through organoselenium intermediates, of commercially available ethyl (R)- and (S)-4-chloro-3-hydroxybutyrate into a protected 1,2-amino alcohol with retention of the original configuration.