625-72-9

Basic information

• Product Name: (R)-3-HYDROXYBUTYRIC ACID
• Synonyms: (R)-(-)-3-HYDROXYBUTYRIC ACID;(R)-3-HYDROXYBUTYRIC ACID;d-beta-hydroxybutyrate;(R)-3-Hydroxybutyrate;D-(-)-3-Hydroxybutyrate;D(-)-3-Hydroxybutyrate;D-3-Hydroxybutyric acid;(R)-3-Hydroxybutanoic acid
• CAS NO: 625-72-9
• Molecular Formula: C₄H₈O₃
• Molecular Weight: 104.1
• EINECS: 210-909-6
• Product Categories: Carboxylic Acids;Chiral Building Blocks;Organic Building Blocks
• Mol File: 625-72-9.mol
• Article Data: 41

Chemical Properties

• Melting Point: 49-50 °C(lit.)
• Boiling Point: 269.216 °C at 760 mmHg
• Flash Point: 112 °C
• Appearance: white crystal
• Density: 1.195 g/cm³
• Vapor Pressure: 0.000979mmHg at 25°C
• Refractive Index: 1.455
• Storage Temp.: 2-8°C
• PKA: 4.36±0.10(Predicted)
• BRN: 1720568
• CAS DataBase Reference: (R)-3-HYDROXYBUTYRIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3-HYDROXYBUTYRIC ACID(625-72-9)
• EPA Substance Registry System: (R)-3-HYDROXYBUTYRIC ACID(625-72-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• F: 3-10
• Hazardous Substances Data: 625-72-9(Hazardous Substances Data)

Usage

Definition

ChEBI: The R-enantiomer of 3-hydroxybutyric acid. Involved in the synthesis and degradation of ketone bodies, it can be used as an energy source by the brain during hypoglycaemia, and for the synthesis of biodegradable plastics.

InChI:InChI=1/C4H8O3/c1-3(5)2-4(6)7/h3,5H,2H2,1H3,(H,6,7)/t3-/m1/s1

Synthetic route

Methyl (R)-3-hydroxybutyrate (3976-69-0) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
Stage #1: Methyl (R)-3-hydroxybutyrate With potassium hydroxide In water at 0 - 20℃; for 48h; Inert atmosphere; Stage #2: With hydrogenchloride In water pH=1; Inert atmosphere;	94%
With potassium hydroxide In water at 4℃; for 480h;	91%
Stage #1: Methyl (R)-3-hydroxybutyrate With potassium hydroxide; water at 0℃; for 25.5h; Stage #2: With hydrogenchloride; water at 5℃;	87%

sodium (R)-3-hydroxybutyrate (13613-65-5) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With DOWEX 50x8-200 ion-exchange resin In methanol	94%
With hydrogenchloride; water pH=1;	69%
With hydrogenchloride; water

Ethyl (R)-3-hydroxybutanoate (24915-95-5) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With potassium hydroxide at 0℃; for 24h;	93%
With sodium hydroxide In water at 10℃; for 6h;	85%
With potassium hydroxide for 12h; Ambient temperature;

(3'R,4S)-3-(3'-hydroxybutanoyl)-4-(1-methylethyl)-2-oxazolidinone (77877-38-4) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With lithium hydroxide; dihydrogen peroxide In tetrahydrofuran at 20℃; for 1h;	62%
With potassium hydroxide In methanol at 0℃; for 0.75h;

poly<(R)-3-hydroxybutanoic acid> → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With toluene-4-sulfonic acid In methanol; 1,2-dichloro-ethane for 15h; Heating;	54%

ethyl 3-hydroxybutyrate (5405-41-4) → (R)-3-hydroxybutyric acid (625-72-9) + ethyl (S)-3-hydroxybutyrate (56816-01-4)

Conditions	Yield
With sodium hydroxide In water at 30℃; pH=6.9;	A n/a B 36.4%

3-hydroxybutanenitrile (4368-06-3) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With hydrogenchloride

(S)‐3‐chlorobutanoic acid (25139-77-9) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With water

methyl 3-aminobutyrate (6078-06-4) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With cis-nitrous acid Verseifung des Reaktionsproduktes;

(S)-3-chloro-butyric acid methyl ester; methyl ester of/the/ dextrorotatory β-chloro-butyric acid (126575-28-8) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With water

(R)-(-)-3-acetoxybutyric acid (52020-45-8) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With potassium hydroxide

D-glucose (50-99-7) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
Vergaerung auch von anderen Zuckern durch Bac.megatherium (oder andere Mikroorganismen, z.B.Bac.cereus, Bac.polymyxa) bei 30grad und Autolyse der entstandenen intracellulaeren Polysaeure;

2-acetoacetic acid (541-50-4) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
bei der Durchstroemung der ueberlebenden Hundeleber;
in tierischen Geweben unter anaeroben Bedingungen;
With hydrogen in Gegenwart von zellfreies Enzymextrakt aus Clostridium kluyveri;

2,4-dioxo-pentanoic acid (5699-58-1) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
in tierischen Geweben unter anaeroben Bedingungen;

5-ketohexanoic acid (3128-06-1) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
bei der Leberdurchstroemung;

acetic acid (64-19-7) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
bei der Leberdurchstroemung;

hexanoic acid (142-62-1) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
bei der Leberdurchstroemung;

3-Hydroxybutyric acid (300-85-6, 625-71-8) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
durch Pilze;

butyric acid (107-92-6) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
bei der Leberdurchstroemung;

3-Hydroxybutyric acid (300-85-6, 625-71-8) + Quinine (130-95-0) → (R)-3-hydroxybutyric acid (625-72-9)

xanthomegnin (1685-91-2) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
Multistep reaction;

3-<2-Hydroxy-propyl>-2,6-bis-hydroxymethyl-anisol → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
(i) O3, CHCl3, (ii) Ag2O, H2O; Multistep reaction;

5,5,7-OH(3)-Oct-2-enoic Saeure → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With sodium periodate

1.3-butanediol (18826-95-4, 107-88-0) → (S)-3-Hydroxybutanoic Acid (6168-83-8) + (R)-3-hydroxybutyric acid (625-72-9) + 2-acetoacetic acid (541-50-4)

Conditions	Yield
With D-glucose; calcium carbonate at 27℃; for 48h; Hansenula anomala IFO 0195; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With D-glucose; calcium carbonate at 27℃; for 48h; Product distribution; Hansenula anomala IFO 0195, potato-dextrose-agar; other yeasts, influence of glucose, fructose, temperature: stereoselectivity; also with optically active 1,3-butanediol;

2-acetoacetic acid (541-50-4) → (S)-3-Hydroxybutanoic Acid (6168-83-8) + (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With potassium dihydrogenphosphate; baker's yeast; D-glucose In water at 28℃; for 9h; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With potassium dihydrogenphosphate; baker's yeast; D-glucose In water at 28℃; for 9h; Product distribution; other times; other β-keto acids investigated;
With diisopinocampheylborane In tetrahydrofuran at 20℃; for 32h; Title compound not separated from byproducts.;

ethyl acetoacetate (141-97-9) → (S)-3-Hydroxybutanoic Acid (6168-83-8) + (R)-3-hydroxybutyric acid (625-72-9) + Ethyl (R)-3-hydroxybutanoate (24915-95-5) + ethyl (S)-3-hydroxybutyrate (56816-01-4)

Conditions	Yield
With Halobacterium halobium; pepton; potassium chloride; water; sodium citrate; magnesium sulfate; sodium chloride at 40℃; for 120h; Irradiation; Yields of byproduct given. Title compound not separated from byproducts;
With Halobacterium halobium; pepton; potassium chloride; sodium citrate; magnesium sulfate; sodium chloride In water at 40℃; for 120h; Irradiation; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(4R,6S,7S,10R)-7-Isopropyl-4,10-dimethyl-1,5-dioxa-spiro[5.5]undecan-2-one (114701-16-5, 114761-10-3) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With hydrogenchloride In diethyl ether Ambient temperature;

(R)-3-Acetoxybuttersaeure-ethylester (114592-78-8) → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With sodium hydroxide; water 1.) room temp., 2 d; 2.) 4 deg C, 1 d; Yield given. Multistep reaction;

l-menthyl (2R,6R)-2,6-dimethyl-4-oxo-1,3-dioxane-2-carboxylate → (R)-3-hydroxybutyric acid (625-72-9)

Conditions	Yield
With potassium hydroxide In methanol at 50℃; for 0.0833333h;

diazomethane (186581-53-3, 908094-01-9) + (R)-3-hydroxybutyric acid (625-72-9) → Methyl (R)-3-hydroxybutyrate (3976-69-0)

Conditions	Yield
In diethyl ether	100%
In methanol; diethyl ether at -10℃;	76%

(R)-3-hydroxybutyric acid (625-72-9) + tert-butyldimethylsilyl chloride (18162-48-6) → 3-(R)-t-butyldimethylsilyloxybutanoic acid (105729-41-7, 107493-76-5, 101515-46-2)

Conditions	Yield
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 48h; Inert atmosphere;	100%
With dmap; triethylamine In dichloromethane for 36h; Ambient temperature;	84%

(R)-3-hydroxybutyric acid (625-72-9) + triisopropylsilyl trifluoromethanesulfonate (80522-42-5) → methyl 3(R)-butanoate (126249-06-7, 122358-09-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h;	100%

(R)-3-hydroxybutyric acid (625-72-9) + 2-Methoxypropene (116-11-0) → 2,2,6-trimethyl-1,3-dioxane-4-one

Conditions	Yield
Stage #1: (R)-3-hydroxybutyric acid In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: 2-Methoxypropene With Amberlyst 15H In dichloromethane at 20℃; for 2h; Inert atmosphere;	98.8%

chloro-trimethyl-silane (75-77-4) + (R)-3-hydroxybutyric acid (625-72-9) → trimethylsilyl (R)-3-<(trimethylsilyl)oxy>butyrate (108438-96-6)

Conditions	Yield
With triethylamine In dichloromethane for 48h; Ambient temperature;	94%
In tetrahydrofuran Heating;

(R)-3-hydroxybutyric acid (625-72-9) + L-α-amino-N-(benzyloxy)caprolactam (77611-42-8) → benzyl cobactin T (77629-24-4)

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline In tetrahydrofuran at 50℃; for 22h;	79%

(R)-3-hydroxybutyric acid (625-72-9) + allyl alcohol (107-18-6) → (R)-3-hydroxybutanoic acid allylester (152996-89-9)

Conditions	Yield
With sulfuric acid In benzene for 4h; Heating;	74%

(R)-3-hydroxybutyric acid (625-72-9) + Octanal (124-13-0) → (2R,6R)-2-heptyl-6-methyl-1,3-dioxan-4-on (99902-24-6)

Conditions	Yield
With Dowex 50*8; pyridinium p-toluenesulfonate In dichloromethane Heating;	71%

(R)-3-hydroxybutyric acid (625-72-9) + Octanal (124-13-0) → (2R,6R)-2-heptyl-6-methyl-1,3-dioxan-4-on (99902-24-6) + (2S,6R)-2-Heptyl-6-methyl-[1,3]dioxan-4-one (99902-24-6)

Conditions	Yield
With pyridinium p-toluenesulfonate In dichloromethane Yields of byproduct given;	A 71% B n/a

(R)-3-hydroxybutyric acid (625-72-9) + benzyl alcohol (100-51-6) → (R)-3-hydroxybutanoic benzyl ester (88280-53-9)

Conditions	Yield
With toluene-4-sulfonic acid In benzene Heating;	71%

C25H26N2O2 (957208-91-2) + (R)-3-hydroxybutyric acid (625-72-9) → C29H32N2O4 (957208-92-3)

Conditions	Yield
With 4-methyl-morpholine; 1-hydroxy-7-aza-benzotriazole; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide In chloroform at 20℃; for 1h;	70%

(R)-3-hydroxybutyric acid (625-72-9) + (S)-2-(benzyloxy)propanal (81445-44-5) → (2R,6R)-2-<1-(S)-benzyloxyethyl>-6-methyl-1,3-dioxan-4-one (127680-52-8)

Conditions	Yield
With pyridinium p-toluenesulfonate In dichloromethane Heating;	69%

3-phenyl-propionaldehyde (104-53-0) + (R)-3-hydroxybutyric acid (625-72-9) → (2R,6R)-6-methyl-2-(2'-phenylethyl)-1,3-dioxan-4-on (99902-26-8)

Conditions	Yield
With Dowex 50*8; pyridinium p-toluenesulfonate In dichloromethane Heating;	66%
With pyridinium p-toluenesulfonate In dichloromethane Heating;

3-phenyl-propionaldehyde (104-53-0) + (R)-3-hydroxybutyric acid (625-72-9) → (2R,6R)-6-methyl-2-(2'-phenylethyl)-1,3-dioxan-4-on (99902-26-8) + (2S,6R)-6-Methyl-2-phenethyl-[1,3]dioxan-4-one (112463-39-5)

Conditions	Yield
With pyridinium p-toluenesulfonate In dichloromethane Yields of byproduct given;	A 66% B n/a

nonan-1-al (124-19-6) + (R)-3-hydroxybutyric acid (625-72-9) → (2R,6R)-6-methyl-2-octyl-1,3-dioxan-4-on (99902-25-7) + (2S,6R)-6-methyl-2-octyl-1,3-dioxan-4-on (112463-27-1)

Conditions	Yield
With Dowex 50*8; pyridinium p-toluenesulfonate In dichloromethane Heating;	A 66% B n/a
With pyridinium p-toluenesulfonate In dichloromethane Yield given. Yields of byproduct given. Title compound not separated from byproducts;

(R)-3-hydroxybutyric acid (625-72-9) + 5-[1-(2-fluorophenyl)-1H-indazol-4-yl]hexahydropyrrolo[3,4-b]pyrrol-6-(1H)-one → (3aR,6aR)-5-[1-(2-fluorophenyl)-1H-indazol-4-yl]-1-[(3R)-3-hydroxybutanoyl]hexahydropyrrolo[3,4-b]pyrrol-6(1H)-one

Conditions	Yield
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl-formamide at 40℃; for 1h;	65%

(R)-3-hydroxybutyric acid (625-72-9) + [(S)-1-(tert-Butyl-diphenyl-silanyloxy)-2-oxo-azepan-3-yl]-carbamic acid benzyl ester (171287-62-0) → (R)-N-[(S)-1-(tert-Butyl-diphenyl-silanyloxy)-2-oxo-azepan-3-yl]-3-hydroxy-butyramide (171287-63-1)

Conditions	Yield
With dmap; 4-(dimethylamino)pyridine hydrochloride; dicyclohexyl-carbodiimide In chloroform at 40℃; for 0.5h;	63%

(S)-3-amino-1-(benzyloxy)azepan-2-one hydrobromide (1007123-23-0) + (R)-3-hydroxybutyric acid (625-72-9) → benzyl cobactin T (77629-24-4)

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In acetonitrile at 22℃; for 25h; Inert atmosphere;	62%

(R)-3-hydroxybutyric acid (625-72-9) + isobutyraldehyde (78-84-2) → (2R,6R)-2-isopropyl-6-methyl-1,3-dioxan-4-on (100017-85-4) + (2S,6R)-2-isopropyl-6-methyl-1,3-dioxan-4-on (112530-85-5)

Conditions	Yield
With pyridinium p-toluenesulfonate In benzene Yields of byproduct given;	A 61% B n/a
With Amberlyst; Dowex 50*8; pyridinium p-toluenesulfonate In benzene Heating;	A 61% B n/a

Upstream product

• 25139-77-9 (S)‐3‐chlorobutanoic acid 
• 142-62-1 hexanoic acid 
• 1685-91-2 xanthomegnin 
• 623-58-5 sodium aceto-acetate 
• 3483-11-2 lithium acetoacetate 
• 107-89-1 acetaldol 
• 4368-06-3 3-hydroxybutanenitrile 
• 5405-41-4 ethyl 3-hydroxybutyrate 
• 3976-69-0 Methyl (R)-3-hydroxybutyrate 

Downstream Products

• 24915-95-5 Ethyl (R)-3-hydroxybutanoate 
• 541-50-4 2-acetoacetic acid 
• 99902-26-8 (2R,6R)-6-methyl-2-(2'-phenylethyl)-1,3-dioxan-4-on 
• 112463-39-5 (2S,6R)-6-Methyl-2-phenethyl-[1,3]dioxan-4-one 
• 142337-89-1 (1R,6R)-6-methyl-2-styryl-1,3-dioxan-4-one 
• 145220-46-8 3(R)-(4-Carboxy-2-nitrophenoxy)butyric acid 
• 131991-73-6 (2R,6R)-2--6-methyl-1,3-dioxan-4-one 
• 139764-53-7 (2S,6R)-2--6-methyl-1,3-dioxan-4-one 
• 127680-52-8 (2R,6R)-2-<1-(S)-benzyloxyethyl>-6-methyl-1,3-dioxan-4-one 
• 77629-24-4 benzyl cobactin T 
• 17299-07-9 (2R,5R)-2,5-hexanediol 
• 108053-20-9 (2S,3S)-2-((R)-1-Hydroxy-ethyl)-3-(4-methoxy-benzylamino)-5-trimethylsilanyl-pent-4-ynethioic acid S-phenyl ester 
• 139629-08-6 (4R,8R,12R)-4,8,12-trimethyl-1,5,9-trioxacyclododecane-2,6,10-trione 
• 116761-21-8 (4R,8R,12R,16R,20R)-4,8,12,16,20-pentamethyl-1,5,9,13,17-pentaoxacycloicosane-2,6,10,14,18-pentone 

Relevant articles and documents

PANTETHEINE DERIVATIVES AND USES THEREOF

The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.

Synthesis process of (R)-3-hydroxybutyric acid and salts thereof

The invention discloses a synthesis process for preparing (R)-3-hydroxybutyric acid and sodium salt, potassium salt, magnesium salt and calcium salt thereof. The process includes steps: adding 3-oxobutanoate and a ruthenium complex catalyst into organic solvent according to a mole ratio of 1:0.0005-0.005, and reacting at 20-80 DEG C for 12-24h under a hydrogen pressure of 1-20bar to obtain (R)-3-hydroxybutyrate; dissolving (R)-3-hydroxybutyrate into water, and subjecting to reaction with sodium hydroxide, potassium hydroxide or calcium hydroxide for 2-12h at a low temperature to obtain sodium salt, potassium salt, magnesium salt and calcium salt of (R)-3-hydroxybutyric acid; subjecting water solution of (R)-3-sodium hydroxybutyrate to 732 cation exchange resin treatment to remove sodium ions to obtain (R)-3-hydroxybutyric acid; subjecting (R)-3-hydroxybutyric acid to reaction with magnesium hydroxide to obtain (R)-3-magnesium hydroxybutyrate. Ee values of (R)-3-hydroxybutyric acid and sodium salt, potassium salt, magnesium salt and calcium salt thereof reach 90% or above. The method has advantages of low environment pollution, low cost and easiness in aftertreatment.

A high throughput screening strategy for the assessment of nitrile-hydrolyzing activity towards the production of enantiopure β-hydroxy acids

Nitrile hydrolysing enzymes have found wide use in the pharmaceutical industry for the production of fine chemicals. This work presents a strategy that facilitates the rapid identification of bacterial isolates demonstrating nitrile hydrolysing activity. The strategy incorporates toxicity, starvation and induction studies along with subsequent colorimetric screening for activity, further focusing the assessment towards the substrates of interest. This high-throughput strategy uses a 96 well plate system, and has enabled the rapid biocatalytic screening of 256 novel bacterial isolates towards β-hydroxynitriles. Results demonstrate the strategy's potential to rapidly assess a variety of β-hydroxynitriles including aliphatic, aromatic and dinitriles. A whole cell catalyst Rhodococcus erythropolis SET1 was identified and found to catalyse the hydrolysis of 3-hydroxybutyronitrile with remarkably high enantioselectivity under mild conditions, to afford (S)-3-hydroxybutyric acid in 42% yield and >99.9% ee. The biocatalytic capability of this strain including the variation of parameters such as temperature and time were further investigated and all results indicate the presence of a highly enantioselective if not enantiospecific nitrilase enzyme within the microbial whole cell.