7013-05-0

Usage

Uses

Used in Pharmaceutical Industry:
(S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID is used as an anticonvulsant for the treatment of epilepsy. It functions by binding to the GABAB receptor, which helps in controlling seizures and managing the symptoms of epilepsy.
Used in Research and Development:
(S)-(+)-4-AMINO-3-HYDROXYBUTANOIC ACID is also utilized in research and development for its potential applications in various fields, such as neuroscience and pharmacology. Its unique chemical properties and biological activity make it a valuable compound for studying the mechanisms of neurological disorders and developing new therapeutic strategies.

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

• 132882-98-5 (-)-ethyl 3-cyano-3-hydroxypropionate 
• 83349-20-6 4-<(Benzyloxycarbonyl)amino>-3-hydroxybutanoic acid 
• 109462-43-3 3,4 epoxybutyric acid 
• 851387-87-6 [(5S)-2-oxo-1,3-oxazolidin-5-yl]acetic acid 
• 111607-76-2 acide (S)-benzamido-4 hydroxy-3 butanoique 
• 116332-79-7 N-(<(2R,4S)-2-(tert-butyl)-6-oxo-1,3-dioxan-4-yl>methyl)acetamide 
• 99475-69-1 (S)-3-tert-Butoxy-4-tert-butoxycarbonylamino-butyric 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 
• 95574-97-3 (R)-(-)-4-chloro-3-hydroxybutanoic acid 

Downstream Products

• 68108-18-9 (4S)-4-hydroxypyrrolidin-2-one 
• 111607-77-3 (S)-hydroxy-4 phenylacetyl-1 pyrrolidinone-2 
• 99211-78-6 (S)-4-Dimethylamino-3-hydroxy-butyric acid 
• 1455087-62-3 (S)-4-(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-3-hydroxybutanoic acid 
• 130239-34-8 4-Aminobutan-1,3-diol 
• 127852-78-2 (S)-4-((tert-butoxycarbonyl)amino)-3-hydroxybutanoic acid 

Relevant academic research and scientific papers

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.

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

Stereoselective synthesis of (S)-oxiracetam and (S)-GABOB from (R)-glyceraldehyde acetonide

Synthetic routes to (S)-oxiracetam and (S)-GABOB have been developed starting from (R)-glyceraldehyde acetonide through its conversion to an appropriate aldehyde intermediate followed by reductive amination using glycinamide hydrochloride/benzyl amine and subsequent chemical transformations.

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.

Asymmetric synthesis of (S)-(+)-carnitine and analogs

A general asymmetric route to enantiomerically pure (S)-(+)-carnitine and analogs has been investigated that involves mono-addition of organometallic reagents to the lactone carbonyl group of (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin- 2-one and Lewis acid promoted stereoselective allylation of the resulting hemiacetals. The diastereomerically pure allyl oxazines thus obtained were readily converted into enantiomerically pure (S)-(+)-carnitine and two substituted analogs.

Efficient syntheses of (S)-4-hydroxy-2-pyrrolidinone derivatives

Efficient syntheses of (S)-4-hydroxy-2-pyrrolidinone ((5)-2) and (R)4- acetylthio-2-pyrrolidinone (S), which are key intermediates of oral carbapenem CS-834, were studied. The most efficient route to (S)-2 from (S)- 3-hydroxybutyrolactone (8) was accomplished in high yield via (S)-N-allyl-3- (1-ethoxy)ethoxy-4-hydroxybutyramide (14).

General asymmetric synthesis of hydroxymethylene and hydroxyethylene peptide isosteres

The Lewis acid-promoted coupling reactions of (5R, 6S)-2-acetoxy-4- (benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazines (11a-e, and 21), which are prepared easily from (+)-(5R, 6S)-4(benzyloxycarbonyl)- 5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (9), with allyltrimethylsilane proceeded to give the corresponding coupling products with moderate to excellent stereoselectivity in good yields. These coupling products (13a, b, and d) were converted to hydroxymethylene-(25a, b, and d) and hydroxyethylene (28) peptide isosteres.

A convenient preparation of optically pure 3-hydroxyglutaric acid derivatives

The diastereomeric monoamides resulting from condensation of (L)-cysteine with 3-hydroxyglutarodinitrile have been separted by chromatography then transformed in a few steps into either (+) or (-) methyl ester of 4-cyano-3-hydroxybutyric acid.

A simple total synthesis of naturally occurring hydroxy-amino acids by enzymatic kinetic resolution

Both optically pure enantiomers of GABOB and isoserine were obtained by enzymatic kinetic resolution of acetylated precursors in three or four steps. The key intermediates were cyanohydrins available from simple aldehydes. This procedure can be applied to other unusual hydroxy amino acids widely distributed in biologically important peptides.