32328-03-3

Basic information

• Product Name: Diethyl 3-hydroxyglutarate
• Synonyms: 3-HYDROXYGLUTARIC ACID DIETHYL ESTER;DIETHYL 3-HYDROXYGLUTARATE;DIETHYL-BETA-HYDROXYGLUTARATE;Diethyl 3-hydroxypentanedioate;Pentanedioic acid, 3-hydroxy-, diethyl ester;Pentanedioic acid, 3-hydroxy-, 1,5-diethyl ester;Einecs 250-992-6;Diethyl 3-hydroxyglu
• CAS NO: 32328-03-3
• Molecular Formula: C₉H₁₆O₅
• Molecular Weight: 204.22
• EINECS: 250-992-6
• Product Categories: C8 to C9;Carbonyl Compounds;Esters;Building Blocks;C8 to C9;Carbonyl Compounds;Chemical Synthesis;Organic Building Blocks
• Mol File: 32328-03-3.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 156-157 °C23 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Light yellow to colorless liquid
• Density: 1.103 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.00229mmHg at 25°C
• Refractive Index: n20/D 1.439(lit.)
• Storage Temp.: Sealed in dry,Room Temperature
• PKA: 13.60±0.20(Predicted)
• BRN: 1709448
• CAS DataBase Reference: Diethyl 3-hydroxyglutarate(CAS DataBase Reference)
• NIST Chemistry Reference: Diethyl 3-hydroxyglutarate(32328-03-3)
• EPA Substance Registry System: Diethyl 3-hydroxyglutarate(32328-03-3)

Safety Data

• Safety Statements: 23-24/25
• WGK Germany: 3
• Hazardous Substances Data: 32328-03-3(Hazardous Substances Data)

Usage

InChI:InChI=1/C9H16O5/c1-3-13-8(11)5-7(10)6-9(12)14-4-2/h7,10H,3-6H2,1-2H3

Synthetic route

diethyl 1,3-acetonedicarboxylate (105-50-0) → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
With sodium tetrahydroborate; ethanol at 0℃; for 0.05h;	95%
With sodium amalgam
With 1,4-dioxane; nickel Hydrogenation;

diethyl 3-hydroxypentanedioate (638-18-6) + ethanol (64-17-5) → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
With sulfuric acid
With sulfuric acid

ethanol (64-17-5) + 3-hydroxyglutaronitrile (13880-89-2) → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
With sulfuric acid at 90 - 100℃;
With hydrogenchloride In diethyl ether

3-hydroxyglutaronitrile (13880-89-2) → diethyl 3-hydroxyglutarate (32328-03-3)

allyl bromide (106-95-6) + diethyl 1,3-acetonedicarboxylate (105-50-0) → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
With sodium ethanolate 1.) EtOH, r.t., overnight, 2.) baker's yeast, H2O, 30 deg C, 72 h; Yield given. Multistep reaction;

diethyl 1,3-acetonedicarboxylate (105-50-0) + Raney nickel → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
Hydrogenation;

ethanol (64-17-5) + triethylamine (121-44-8) + diethyl 1,3-acetonedicarboxylate (105-50-0) + Raney nickel → diethyl 3-hydroxyglutarate (32328-03-3) + pentane-1,3,5-triol (4328-94-3)

Conditions	Yield
at 125℃; under 250073 Torr; Hydrogenation;

acetonedicarboxylic acid (542-05-2) → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
Multi-step reaction with 2 steps 2: sodium amalgam View Scheme

3-oxopentanedioic acid dimethyl ester (1830-54-2) → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaBH4 / methanol 2: KOH / methanol 3: H2SO4 View Scheme

dimethyl 3-hydroxypentanedioate (7250-55-7) → diethyl 3-hydroxyglutarate (32328-03-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: KOH / methanol 2: H2SO4 View Scheme

diethyl 3-hydroxyglutarate (32328-03-3) + 1-(Trimethylsilyl)imidazole (18156-74-6) → diethyl 3-<(trimethylsilyl)oxy>pentanedioate (91424-41-8)

Conditions	Yield
In dichloromethane for 26.5h; Ambient temperature;	100%
for 12.5h; Ambient temperature;

diethyl 3-hydroxyglutarate (32328-03-3) + tert-butyldimethylsilyl chloride (18162-48-6) → 3-[[(1,1-Dimethylethyl)dimethylsilyl]-oxy]pentanedioic acid,diethyl ester (91424-39-4)

Conditions	Yield
With 1H-imidazole In dichloromethane Inert atmosphere;	99%
With 1H-imidazole In dichloromethane	99%
With 1H-imidazole In dichloromethane for 18h; Ambient temperature;	95%

chloro-trimethyl-silane (75-77-4) + diethyl 3-hydroxyglutarate (32328-03-3) → diethyl 3-<(trimethylsilyl)oxy>pentanedioate (91424-41-8)

Conditions	Yield
With 1H-imidazole In dichloromethane at 20℃; Inert atmosphere;	99%
With 1H-imidazole In dichloromethane at 20℃;	99%
With 1H-imidazole In dichloromethane at 20 - 25℃; for 16h; Inert atmosphere;

diethyl 3-hydroxyglutarate (32328-03-3) → (3S)-5-ethoxy-3-hydroxy-5-oxopentanoic acid (95310-87-5)

Conditions	Yield
With Candida antarctica lipase B; water; sodium hydroxide at 40℃; for 0.5h; pH=7; Kinetics; pH-value; Temperature; Concentration; aq. phosphate buffer; optical yield given as %ee; enantioselective reaction;	98.5%
With Esterase 30 000 In cyclohexane; water at 25℃; for 3h; pH 7.5 (0.1 M phosphat buffer);	94%
With Arthrobacter sp (ATCC 19140) In various solvent(s) for 48h; Product distribution; Microorganism: Corynebacterium equi. Object: enantioselective hydrolysis;	38%
In various solvent(s) for 48h; Corynebacterium equi (IFO-3730) or Arthrobacter sp (ATCC 19140); Yield given;
With lipase B from Candida antarctica at 20℃; for 1h; pH=7; aq. phosphate buffer; Inert atmosphere; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;

diethyl 3-hydroxyglutarate (32328-03-3) → pentane-1,3,5-triol (4328-94-3)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 66℃; for 72h; Inert atmosphere;	97%
Stage #1: diethyl 3-hydroxyglutarate With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 20℃; Stage #2: With ammonium chloride In tetrahydrofuran at -78℃; Cooling with acetone-dry ice;	78%
With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 3h;	65%

diethyl 3-hydroxyglutarate (32328-03-3) + Methoxyacetyl chloride (38870-89-2) → 3-(2-Methoxy-acetoxy)-pentanedioic acid diethyl ester (483299-14-5)

Conditions	Yield
With pyridine In dichloromethane at 20℃;	97%

diethyl 3-hydroxyglutarate (32328-03-3) + tert-butylchlorodiphenylsilane (58479-61-1) → 3-(tert-butyldiphenylsilanyloxy)pentanedioic acid diethyl ester (923027-81-0)

Conditions	Yield
With 1H-imidazole In dichloromethane at 20℃; for 16h;	96%

diethyl 3-hydroxyglutarate (32328-03-3) → (S)-3-hydroxyglutaric acid monoamidemonoethyl ester

Conditions	Yield
Novozym 435	95%

diethyl 3-hydroxyglutarate (32328-03-3) + allyl ethyl carbonate (1469-70-1) → diethyl 3-(allyloxy)glutarate

Conditions	Yield
With bis(η3-allyl-μ-chloropalladium(II)); 1,4-di(diphenylphosphino)-butane In toluene at 110℃; for 16h; Inert atmosphere;	95%

diethyl 3-hydroxyglutarate (32328-03-3) + benzaldehyde (100-52-7) → diethyl 3-(benzyloxy)pentanedioate (838906-52-8)

Conditions	Yield
Stage #1: diethyl 3-hydroxyglutarate; benzaldehyde With Hexamethyldisiloxane; trimethylsilyl trifluoromethanesulfonate In tetrahydrofuran at -30℃; for 2h; Inert atmosphere; Stage #2: With triethylsilane In tetrahydrofuran at -30℃; for 16h; Inert atmosphere; Stage #3: With sodium tetrahydroborate In methanol at 0℃; for 1h; Inert atmosphere;	93%
Stage #1: diethyl 3-hydroxyglutarate; benzaldehyde With trimethylsilyl trifluoromethanesulfonate; C6H18OSSi In tetrahydrofuran for 2h; Cooling; Stage #2: With triethylsilane In tetrahydrofuran for 16h; Cooling; Stage #3: With methanol; sodium tetrahydroborate at 0℃; for 1h;	93%

diethyl 3-hydroxyglutarate (32328-03-3) → 3-hydroxyglutaramide (16072-48-3)

Conditions	Yield
With ammonia In methanol at 20℃; for 144h;	90%
With ammonia

methanol (67-56-1) + diethyl 3-hydroxyglutarate (32328-03-3) → dimethyl 3-hydroxypentanedioate (7250-55-7)

Conditions	Yield
scandium tris(trifluoromethanesulfonate) at 64℃; for 24h;	89%

diethyl 3-hydroxyglutarate (32328-03-3) + acetic anhydride (108-24-7) → ethyl 3-acetoxypentanedioate (91967-12-3)

Conditions	Yield
With pyridine Ambient temperature;	88%

Benzyloxymethyl chloride (3587-60-8) + diethyl 3-hydroxyglutarate (32328-03-3) → diethyl 3-(benzyloxymethyloxy)glutarate (1607830-30-7)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere;	85%
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	85%
With tetrabutyl-ammonium chloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h;	60%

diethyl 3-hydroxyglutarate (32328-03-3) → diethyl 3-hydroxypentanedioate (638-18-6)

Conditions	Yield
With sodium hydroxide In methanol; water for 60h; Ambient temperature;	84%
With potassium hydroxide In ethanol

diethyl 3-hydroxyglutarate (32328-03-3) + β-naphthaldehyde (66-99-9) → diethyl 3-(naphth-2-yl-methoxy)glutarate

Conditions	Yield
Stage #1: diethyl 3-hydroxyglutarate; β-naphthaldehyde With Hexamethyldisiloxane; trimethylsilyl trifluoromethanesulfonate In tetrahydrofuran at -30℃; for 2h; Inert atmosphere; Stage #2: With triethylsilane In tetrahydrofuran at -30℃; for 16h; Inert atmosphere; Stage #3: With sodium tetrahydroborate In methanol at 0℃; for 1h; Inert atmosphere;	82%
Stage #1: diethyl 3-hydroxyglutarate; β-naphthaldehyde With trimethylsilyl trifluoromethanesulfonate; C6H18OSSi In tetrahydrofuran for 2h; Cooling; Stage #2: With triethylsilane for 16h; Cooling; Stage #3: With methanol; sodium tetrahydroborate at 0℃; for 1h;	82%

diethyl 3-hydroxyglutarate (32328-03-3) + methyl iodide (74-88-4) → diethyl 3-methoxypentanedioate

Conditions	Yield
With silver(l) oxide In N,N-dimethyl-formamide at 20℃; for 72h;	82%

diethyl 3-hydroxyglutarate (32328-03-3) + O-benzyl 2,2,2-trichloroacetimidate (81927-55-1) → diethyl 3-(benzyloxy)pentanedioate (838906-52-8)

Conditions	Yield
With trifluorormethanesulfonic acid In dichloromethane; cyclohexane at 0℃; for 24h;	79%
With trifluorormethanesulfonic acid In dichloromethane; cyclohexane at 20℃; for 20h; Inert atmosphere;	78%

diethyl 3-hydroxyglutarate (32328-03-3) + (4-chlorophenyl)(pyridin-2-yl)methyl 2,2,2-trichloroacetimidate → diethyl 3-[(4-chlorophenyl)(pyridin-2-yl)methoxy]pentanedioate

Conditions	Yield
With copper(II) bis(trifluoromethanesulfonate) In dichloromethane at 20℃; for 24h; Molecular sieve; Inert atmosphere; Cooling with ice;	73%

diethyl 3-hydroxyglutarate (32328-03-3) + tert-butyldimethylsilyl chloride (18162-48-6) → 3-(tert-Butyl-dimethyl-silanyloxy)-pentanedioic acid (113794-48-2)

Conditions	Yield
Stage #1: tert-butyldimethylsilyl chloride With 1H-imidazole In dichloromethane at 20 - 30℃; for 1 - 2h; Stage #2: diethyl 3-hydroxyglutarate In dichloromethane at 20 - 30℃; for 4 - 6h; Stage #3: With hydrogenchloride; sodium hydroxide; water more than 3 stages;	71%

diethyl 3-hydroxyglutarate (32328-03-3) → (3R)-5-ethoxy-3-hydroxy-5-oxopentanoic acid (95310-88-6)

Conditions	Yield
With Acinetobacter lowfii In various solvent(s) for 48h; Product distribution; Microrganism: Soil isolate S-29. Object: enantioselective hydrolysis.;	70%
With disodium hydrogenphosphate; α-chymotrypsin
In various solvent(s) for 48h; Acinetobacter lowfii, or Soil isolate S-29; Yield given;
Multi-step reaction with 3 steps 1: zinc perchlorate / 2 h / 20 °C 2: α-chymotrypsin / aq. buffer / 27 h / 20 °C / pH 8 / Enzymatic reaction 3: immobilized Cephalosporin C acetyl esterase / aq. buffer / 20 °C / pH 8 / Enzymatic reaction View Scheme

diethyl 3-hydroxyglutarate (32328-03-3) + S-ethyl 3-phenylpropionic acid thioester (30911-16-1) → 3-(3-Phenyl-propionyloxy)-pentanedioic acid diethyl ester (130260-30-9)

Conditions	Yield
With lithium tetrafluoroborate In acetonitrile Ambient temperature; Pt-electrodes, 50 mA;	64%

diethyl 3-hydroxyglutarate (32328-03-3) + chloromethyl methyl ether (107-30-2) → diethyl 3-(methoxymethoxy)glutarate

Conditions	Yield
With tetrabutyl-ammonium chloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16h;	64%

diethyl 3-hydroxyglutarate (32328-03-3) + but-2-ynyl 2,2,2-trichloroacetimidate (59402-95-8) → diethyl 3-(but-2-yn-1yloxy)glutarate

Conditions	Yield
With trimethylsilyl trifluoromethanesulfonate In dichloromethane at 20℃; for 1h;	60%

diethyl 3-hydroxyglutarate (32328-03-3) + acetoacetic acid methyl ester (105-45-3) → methyl 1,8-dihydroxy-3-(methoxycarbonylmethyl)naphthalene-2-carboxylate (107182-04-7)

Conditions	Yield
Stage #1: diethyl 3-hydroxyglutarate; acetoacetic acid methyl ester With lithium diisopropyl amide In tetrahydrofuran at -78℃; Claisen condensation; Stage #2: With calcium acetate In tetrahydrofuran; methanol	57%
With n-butyllithium; calcium acetate; sodium hydride 1.) THF, hexane, 1 h, room temperature, 2.) MeOH, 2 h, reflux; Yield given. Multistep reaction;

diethyl 3-hydroxyglutarate (32328-03-3) + 1-(1-imino-2,2,2-trichloroethoxy)-3-methyl-2-butene (104808-44-8) → diethyl 3-(3,3-dimethylallyloxy)glutarate + diethyl 3-(1,1-dimethylallyloxy)glutarate

Conditions	Yield
With scandium tris(trifluoromethanesulfonate) In dichloromethane at 20℃; for 0.5h;	A 42% B 24%

diethyl 3-hydroxyglutarate (32328-03-3) + 3-Phenylpropenol (104-54-1) → C18H24O5

Conditions	Yield
Stage #1: diethyl 3-hydroxyglutarate With 1H-imidazole; chloro-trimethyl-silane Inert atmosphere; Stage #2: 3-Phenylpropenol With triethylsilane; iron(III) chloride Reagent/catalyst; Inert atmosphere;	41%

benzyltrichloroacetimidate + diethyl 3-hydroxyglutarate (32328-03-3) → diethyl 3-(benzyloxy)pentanedioate (838906-52-8)

Conditions	Yield
With trifluorormethanesulfonic acid	35%

diethyl 3-hydroxyglutarate (32328-03-3) + benzyl bromide (100-39-0) → diethyl 3-(benzyloxy)pentanedioate (838906-52-8)

Conditions	Yield
With silver(l) oxide	30%
With silver(l) oxide In acetonitrile for 14h; Heating;	24%

Upstream product

• 638-18-6 diethyl 3-hydroxypentanedioate 
• 64-17-5 ethanol 
• 13880-89-2 3-hydroxyglutaronitrile 
• 105-50-0 diethyl 1,3-acetonedicarboxylate 
• 1830-54-2 3-oxopentanedioic acid dimethyl ester 
• 7250-55-7 dimethyl 3-hydroxypentanedioate 
• 542-05-2 acetonedicarboxylic acid 
• 121-44-8 triethylamine 
• 106-95-6 allyl bromide 

Downstream Products

• 98-78-2 3-Oxo-cyclopentanecarboxylic acid 
• 73178-43-5 (E)-diethyl glutaconate 
• 73192-75-3 (Z)-diethyl pent-2-enedioate 
• 1724-02-3 glutaconic acid 
• 90722-08-0 3-bromo-glutaric acid diethyl ester 
• 91424-39-4 3-[[(1,1-Dimethylethyl)dimethylsilyl]-oxy]pentanedioic acid,diethyl ester 
• 678182-81-5 5-[(4-methoxy-phenyl)-diphenyl-methoxy]-pentane-1,3-diol 
• 678182-82-6 1-(tert-butyl-dimethyl-silanyloxy)-5-[(4-methoxy-phenyl)-diphenyl-methoxy]-pentan-3-ol 
• 678182-83-7 1-(tert-butyl-dimethyl-silanyloxy)-5-[(4-methoxy-phenyl)-diphenyl-methoxy]-pentan-3-one 
• 678182-86-0 3-benzoyl-1-{3-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-5-[(4-methoxy-phenyl)-diphenyl-methoxy]-pent-2-enyl}-5-methyl-1H-pyrimidine-2,4-dione 
• 678182-80-4 3-benzoyl-1-{3-[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-2-fluoro-5-[(4-methoxy-phenyl)-diphenyl-methoxy]-pent-2-enyl}-5-methyl-1H-pyrimidine-2,4-dione 
• 312745-91-8 (S)-3-hydroxy-4-cyanobutyric acid ethyl ester 
• 91424-40-7 3-(tert-butyldimethylsilyloxy)glutaric anhydride 
• 113794-48-2 3-(tert-Butyl-dimethyl-silanyloxy)-pentanedioic acid 

Relevant articles and documents

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A class of chiral beta-hydroxyamide compounds, preparation method and applications thereof,

The invention discloses a chiral beta-hydroxyamide compound and a preparation method thereof, wherein the compound is represented by a formula I. According to the invention, the raw material for preparing a non-natural chiral amino acid compound is obtained by carrying out catalytic hydrolysis on a prochiral diamide compound II with different substituents by using a Rhodococcus erythropolis AJ270microbial system, wherein the use amount of the Rhodococcus erythropolis can be adjusted according to the use amount of a substrate, the reaction solvent is a common buffer solution with the pH valueof 6.0-8.0, the temperature is 20-37 DEG C, the reaction time is 3-120 h, and the Rhodococcus erythropolis microbial catalytic system can be cultured through fermentation and conveniently stored; andwith the application of the biotransformation to prepare chiral monoamide carboxylic acid and dicarboxylic acid, the characteristics of simplicity and convenience in operation, high reaction efficiency, mild reaction conditions, high enantioselectivity, easiness in product separation and high product purity are achieved, and the application prospect is god.

Reduction of 2-Substituted 3-Oxoglutarates Mediated by Baker's Yeast. Variation in Enantioselectivity without Corresponding Variation in Diastereoselectivity

The reduction of 2-substituted 3-oxoglutarates by yeast yields a new class of chiral building blocks, 2-allyl- and 2-propargyl-3-hydroxyglutarates.These are useful as starting points for the synthesis of, inter alia, branched chain analogs of sugars and nucleosides.When allyl is the side chain, the principal product has the absolute configuration (2S,3S), proven by correlation with a compound whose absolute configuration was established by crystallography.Several features of this yeast-mediated reduction are noteworthy.First, its diastereoselectivity is higher than its enantioselectivity, especially with the propargyl side chain.Further, with all substrates, variation in enantioselectivity is not manifested by a variation in diastereoselectivity.This example therefore serves as a warning for those using yeast-mediated reactions that diastereoselectivity cannot be accepted as a substitute for direct measurements of enantioselectivity, even with analogous substrates and similar reaction conditions.Finally, an unexpected metabolism of impurities in the starting material by the yeast made the overall transformation preparatively useful.