607-97-6

Basic information

• Product Name: Ethyl 2-ethylacetoacetate
• Synonyms: 2-ethyl-3-oxo-butyricacidethylester;Acetoacetic acid, 2-ethyl-, ethyl ester;Ethyl 2-ethyl-3-ketobutyrate;Ethyl 2-ethyl-3-oxobutanoate;Ethyl alpha-acetylbutyrate;2-Ethyl-3-oxo-butanoic acid ethyl ester;2-ETHYLACETOACETIC ACID ETHYL ESTER;ETHYL 2-ACETYLBUTYRATE
• CAS NO: 607-97-6
• Molecular Formula: C₈H₁₄O₃
• Molecular Weight: 158.19
• EINECS: 210-151-6
• Product Categories: Pharmaceutical Intermediates;Organic acids;API intermediates;C8 to C9;Carbonyl Compounds;Esters
• Mol File: 607-97-6.mol
• Article Data: 32

Chemical Properties

• Melting Point: 170 °C (decomp)
• Boiling Point: 87-189 °C743 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Colorless to pale yellow/Liquid
• Density: 0.981 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.554mmHg at 25°C
• Refractive Index: n20/D 1.421(lit.)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 12.02±0.46(Predicted)
• BRN: 636286
• CAS DataBase Reference: Ethyl 2-ethylacetoacetate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 2-ethylacetoacetate(607-97-6)
• EPA Substance Registry System: Ethyl 2-ethylacetoacetate(607-97-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 23-24/25-36-26
• WGK Germany: 1
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 607-97-6(Hazardous Substances Data)

Usage

Uses

Ethyl 2-ethylacetoacetate was used in the synthesis of 2-alkylidenetetrahydrofurans, diphenyllead(IV) thiosemicarbazonates and pyrazolonates. It was used as starting reagent in the synthesis of 2-ethylfumaric acid.

InChI:InChI=1/C8H14O3/c1-4-7(6(3)9)8(10)11-5-2/h7H,4-5H2,1-3H3/t7-/m1/s1

Synthetic route

ethyl bromide (74-96-4) + ethyl acetoacetate (141-97-9) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With sodium ethanolate In ethanol at -10 - 10℃; for 2h; Inert atmosphere;	94.9%
With potassium carbonate In ethanol; water at 70℃; for 10h; regioselective reaction;	85.3%
With sodium ethanolate	78%

ethyl acetoacetate (141-97-9) + ethyl iodide (75-03-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With sodium In tetrahydrofuran for 20h; Heating;	87%
Stage #1: ethyl acetoacetate With potassium tert-butylate In tetrahydrofuran at 0℃; for 0.5h; Stage #2: ethyl iodide In tetrahydrofuran at 70℃; for 12h; Further stages.;	74%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In benzene for 3h; Ambient temperature;	50%

ethyl acetoacetate (141-97-9) + ethyl iodide (75-03-6) → ethyl 2,2-diethyl-3-oxobutanoate (1619-57-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With P(MeNCH2CH2)3N In hexane; acetonitrile at 0℃; for 0.5h;	A n/a B 78%
With sodium ethanolate 1.) EtOH, 80 deg C, 2.) EtOH, 80 deg C, 2 h; Yield given. Multistep reaction. Yields of byproduct given;
With aluminum oxide; sodium ethanolate 2.) room temperature, 5 d; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With sodium ethanolate 1.) EtOH, 80 deg C, 2.) EtOH, 80 deg C, 2 h; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

diethyl sulfate (64-67-5) + ethyl acetoacetate (141-97-9) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With dimethyl amine at 10 - 15℃;	70%
With sodium ethanolate

diethyl sulfate (64-67-5) + enolate potassique de l'acetylacetate d'ethyle → ethyl (Z)-3-ethoxybut-2-enoate (5331-73-7) + ethyl (E)-3-ethoxy-2-butenoate (57592-45-7) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With polymer-HMPT In tetrahydrofuran at 20℃; for 24h; Yields of byproduct given;	A n/a B 54% C n/a
With copolymere de vinyloxazolidone et de divinylbenzene In tetrahydrofuran at 20℃; for 24h; Yield given. Yields of byproduct given;
With 3-methyl-2-oxo-1,3-oxazolidine In tetrahydrofuran at 20℃; for 24h; Yield given. Yields of byproduct given;
With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran at 20℃; for 24h; Product distribution; further reagents, variation of equivalents of the reagents;

ethyl bromide (74-96-4) + ethyl acetoacetate (141-97-9) → ethyl 3-ethoxy-2-butenoate (998-91-4) + ethyl 2,2-diethyl-3-oxobutanoate (1619-57-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With aluminum oxide; sodium ethanolate 2.) room temperature, 5 d; Yields of byproduct given. Title compound not separated from byproducts;	A n/a B n/a C 53%

ethyl acetoacetate (141-97-9) + diphenylethylsulfonium perchlorate (10504-65-1) → ethyl 3-ethoxy-2-butenoate (998-91-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With potassium carbonate In dichloromethane for 17h; Ambient temperature;	A 10% B 50%

ethyl-α-ethylacetoacetate cyanohydrin (247098-17-5) → 3-amino-3-cyano-2-ethyl-3-methyl-propionic acid ethyl ester + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With hydrogen; nickel In methanol; ammonium hydroxide at 20℃; under 2068.59 - 2327.17 Torr;	A 50% B n/a

ethyl bromide (74-96-4) + 18-crown-6 ether (17455-13-9) + acetoacetic acid ethyl ester; potassium (Z)-enolate (66279-50-3) + [2.2.2]cryptande (23978-09-8) → ethyl (Z)-3-ethoxybut-2-enoate (5331-73-7) + ethyl (E)-3-ethoxy-2-butenoate (57592-45-7) + ethyl 2,2-diethyl-3-oxobutanoate (1619-57-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
In 1,2-dimethoxyethane at 40℃; Mechanism; Product distribution;	A 2% B 8% C n/a D n/a

2-ethyl-3-methyl-pentenedioic acid diethyl ester → oxalic acid (144-62-7) + ethyl acetoacetate (141-97-9) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
bei der Ozonspaltung;

4-ethyl-3-methyl-pentenedioic acid diethyl ester (857819-83-1) → oxalic acid (144-62-7) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
bei der Ozonspaltung;

2-acetyl-3-methyl-succinic acid-1-ethyl ester (90833-10-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
Erhitzen;

ethanol (64-17-5) + ethyl acetoacetate (141-97-9) + ethyl iodide (75-03-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
Reaktion ueber mehrere Stufen;

ethyl bromide (74-96-4) + sodium ethanolate (141-52-6) + ethyl acetoacetate (141-97-9) + diethyl malonate (105-53-3) → ethyl diethyl malonate (133-13-1) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

ethyl 3-methylaminocrotonate (870-85-9) + ethyl iodide (75-03-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
at 100℃; beim folgenden Kochen mit Wasser;
anschliessende Hydrolyse des Reaktionsprodukts mit siedendem Wasser;

ethanol (64-17-5) + sodium ethyl acetylacetate enolate (1007476-32-5) + ethyl iodide (75-03-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

3-diethylamino-crotonic acid ethyl ester (59222-31-0) + ethyl iodide (75-03-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

3-dipropylamino-crotonic acid ethyl ester + ethyl iodide (75-03-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
anschliessende Hydrolyse des Reaktionsprodukts mit siedendem Wasser;

sodium ethyl acetylacetate enolate (1007476-32-5) + ethyl iodide (75-03-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
at 160 - 170℃;
With diethyl ether
With benzene
at 100℃;

sodium ethanolate (141-52-6) + ethyl iodide (75-03-6) + acetoacetic acid methyl ester (105-45-3) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

ethyl iodide (75-03-6) + 3-dimethylamino-crotonic acid ethyl ester (14205-42-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
anschliessenden Hydrolyse mit Wasser;
anschliessende Hydrolyse des Reaktionsprodukts mit siedendem Wasser;

ethyl acetate (141-78-6) + 2-bromobutyric acid ethyl ester (533-68-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With magnesium

Ketene (463-51-4) + 2-bromobutyric acid ethyl ester (533-68-6) → ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With diethyl ether; iodine; zinc

ethyl bromide (74-96-4) + ethyl acetoacetate (141-97-9) → ethyl 3-ethoxy-2-butenoate (998-91-4) + ethyl 2,2-diethyl-3-oxobutanoate (1619-57-4) + 2-Ethyl-3-ethoxy-3-methyl-acrylsaeureethylester (103110-71-0) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
(i) K, EtOH, (ii) /BRN= 1209224/, HMPA; Multistep reaction;

ethyl bromide (74-96-4) + acetoacetic acid ethyl ester; potassium (Z)-enolate (66279-50-3) → ethyl (Z)-3-ethoxybut-2-enoate (5331-73-7) + ethyl (E)-3-ethoxy-2-butenoate (57592-45-7) + ethyl 2,2-diethyl-3-oxobutanoate (1619-57-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With 18-crown-6 ether 1) DME, 40 deg C, 2) DME, 40 deg C; Yield given. Multistep reaction. Yields of byproduct given;

ethyl bromide (74-96-4) + acetoacetic acid ethyl ester; potassium (Z)-enolate (66279-50-3) → ethyl (E)-3-ethoxy-2-butenoate (57592-45-7) + ethyl 2,2-diethyl-3-oxobutanoate (1619-57-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With [2.2.2]cryptande 1) t-BuOH, 40 deg C, 2) t-BuOH, 40 deg C; Yield given. Multistep reaction. Yields of byproduct given;

diethyl sulfate (64-67-5) + C12H34N6O2P2*2C6H9O3(1-)*2Li(1+) (84850-88-4) → ethyl 3-ethoxy-2-butenoate (998-91-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
In dichloromethane for 72h; Product distribution; Ambient temperature; other metal ion, other time, var. addends;	A 46 % Chromat. B 54 % Chromat.

diethyl sulfate (64-67-5) + acetoacetic acid ethyl ester; potassium (Z)-enolate (66279-50-3) → ethyl (Z)-3-ethoxybut-2-enoate (5331-73-7) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
In tetrahydrofuran for 66h; Yield given. Yields of byproduct given;
With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran for 24h; Yield given. Yields of byproduct given;

diethyl sulfate (64-67-5) + enolate lithique de l'acetylacetate d'ethyle (33283-91-9) → ethyl (Z)-3-ethoxybut-2-enoate (5331-73-7) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran for 74h; Yield given. Yields of byproduct given;
With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran for 24h; Yield given. Yields of byproduct given;

diethyl sulfate (64-67-5) + enolate sodique de l'acetylacetate d'ethyle (20412-62-8, 66279-49-0) → ethyl (Z)-3-ethoxybut-2-enoate (5331-73-7) + ethyl 2-ethyl-3-oxobutanoate (607-97-6)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran for 120h; Yield given. Yields of byproduct given;
With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran for 24h; Yield given. Yields of byproduct given;
With Hexamethylphosphorous triamide In tetrahydrofuran for 120h; Product distribution; Ambient temperature; different Li, Na, K enolates, ratios of reagent, reaction times; with solid and liquid and without HMPT;

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 2-ethyl-2-chloro-acetoacetic acid ethyl ester (130000-37-2)

Conditions	Yield
With tetraethylammonium trichloride In dichloromethane	100%
With N-chloro-succinimide; magnesium(II) perchlorate In acetonitrile at 20℃; for 2h;	86%
With chlorine

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl (2R,3S)-2-ethyl-3-hydroxybutanoate (123327-53-7, 5465-11-2, 87519-05-9, 114592-80-2, 123407-56-7, 123407-57-8, 128443-93-6, 128443-94-7)

Conditions	Yield
With D-glucose; ketoreductase-102; NADPH; glucose dehydrogenase; sodium phosphate buffer at 37℃; for 3h; pH=6.9;	100%
With D-glucose; calcium carbonate; sodium chloride In water at 35℃; for 72h; Enzymatic reaction; optical yield given as %ee; enantioselective reaction;	78%
With Escherichia coli strain expressing Gcy1p; isopropyl β-D-thiogalactopyranoside at 20℃; Reduction;	75%
With D-glucose; tris hydrochloride at 30℃; for 48h; β-keto ester reductase L-1, NADPH, GDH;	31%
With glucose-6-phosphate dehydrogenase; α-D-glucose 6-phosphate; baker yeast YDL124w gene-pIK8 plasmid; NAD at 30℃; for 24h; pH=7.0;

[N-(p-tolylsulfonyl)imino]phenyliodinane (55962-05-5) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-acetyl-3-methyl-1-tosylaziridine-2-carboxylate (1373511-29-5)

Conditions	Yield
With 1,10-Phenanthroline; copper(II) bis(trifluoromethanesulfonate) In dichloromethane at 20℃; for 18h; Molecular sieve; Inert atmosphere; optical yield given as %de;	99%

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 4-ethyl-3-methylisoxazol-5(4H)-one (29068-31-3)

Conditions	Yield
With hydroxylamine hydrochloride; sodium acetate In ethanol at 78℃;	99%

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-bromo-2-ethyl-3-oxobutanoate (32116-06-6)

Conditions	Yield
With N-Bromosuccinimide; ammonium acetate In tetrachloromethane at 80℃; for 0.5h;	97%
With sodium hydrogen sulfate; N-Bromosuccinimide; silica gel at 20℃; for 2h;	95%
With ammonium bromide; dihydrogen peroxide; vanadia In dichloromethane; water at 0 - 5℃; for 3h;	94%

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 2-ethyl-1,3-butanediol (66553-17-1)

Conditions	Yield
With lithium aluminium tetrahydride In diethyl ether for 3h; Heating;	96%
With methanol; copper chromite at 150 - 168℃; Hydrogenation.unter Druck;
With copper chromite; ethanol at 150 - 168℃; Hydrogenation.unter Druck;

N-hydroxyphthalimide (524-38-9) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-(N-phthalimidyloxy)-2-ethyl-3-oxobutanoate

Conditions	Yield
Stage #1: N-hydroxyphthalimide; ethyl 2-ethyl-3-oxobutanoate With cobalt(II) diacetate tetrahydrate In acetic acid at 60℃; for 0.0166667h; Stage #2: With potassium permanganate In acetic acid at 60℃; for 0.175h;	94%

2-methylbenzene-1,3-diol (608-25-3) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 3-ethyl-7-hydroxy-4,8-dimethyl-2H-1-benzopyran-2-one (31575-15-2)

Conditions	Yield
With perchloric acid at 20℃; Pechmann condensation;	92%
With sulfuric acid at 0℃; for 12h; Pechmann Condensation;
With sulfuric acid at 0℃; Pechmann Condensation;

ethylene glycol (107-21-1) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 2-ethoxycarbonylmethyl-2-methyl-1,3-dioxolane (27773-10-0)

Conditions	Yield
With toluene-4-sulfonic acid In toluene at 120℃; for 4h; Product distribution / selectivity;	91%
With toluene-4-sulfonic acid In toluene at 120℃; for 4h; Heating / reflux;	91%
With toluene-4-sulfonic acid In toluene for 3.5h; Cyclization; Heating;	70%

phenylhydrazine (100-63-0) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 4-ethyl-3-methyl-1-phenylpyrazol-5-one (22717-41-5)

Conditions	Yield
for 0.05h; microwave irradiation;	91%
In ethanol Reflux;

tert-Butyl N-hydroxycarbamate (36016-38-3) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → C13H23NO6

Conditions	Yield
With copper(II) acetate hydrate; 2-ethyl-1,3-oxazoline; copper(l) chloride In isopropyl alcohol at 20℃; regioselective reaction;	90%

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 3-methyl-4-ethyl-5-pyrazolone (29211-62-9)

Conditions	Yield
With hydrazine for 0.00833333h;	89%
With hydrazine hydrate; acetic acid In methanol at 100℃; for 1h;	67%

4-methoxy-aniline (104-94-9) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → C15H21NO3

Conditions	Yield
ammonium cerium(IV) nitrate In ethanol at 20℃; for 1.5h;	89%

orcinol (504-15-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 3-ethyl-7-hydroxy-4,5-dimethyl-2H-1-benzopyran-2-one

Conditions	Yield
With perchloric acid at 20℃; Pechmann condensation;	89%

2,2-dibromo-5,5-dimethylcyclohexane-1,3-dione (21428-65-9) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → α-bromo-2-ethyl-3-oxobutyryc acid ethyl ester + 2-bromodimedone (1195-91-1)

Conditions	Yield
Stage #1: ethyl 2-ethyl-3-oxobutanoate With L-Norvaline In dichloromethane for 0.0833333h; Stage #2: 2,2-dibromo-5,5-dimethylcyclohexane-1,3-dione With dipyridinium dichromate In dichloromethane for 2h; Cooling with ice; optical yield given as %ee; enantioselective reaction;	A 88% B n/a

ethyl (2S,3R)-3-(methoxymethyloxy)-2-methylbutanoate + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl (6S,7R)-2-ethyl-3,5-dihydroxy-7-(methoxymethyloxy)-6-methylocta-2,4-dienoate

Conditions	Yield
Stage #1: ethyl 2-ethyl-3-oxobutanoate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Claisen Condensation; Stage #2: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.266667h; Claisen Condensation; Stage #3: ethyl (2S,3R)-3-(methoxymethyloxy)-2-methylbutanoate In tetrahydrofuran; hexane at 0℃; for 0.25h; Claisen Condensation;	88%

ethyl (2R, 3S)-3-(methoxymethyloxy)-2-methylbutanoate + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → C15H26O6

Conditions	Yield
Stage #1: ethyl 2-ethyl-3-oxobutanoate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Stage #2: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.266667h; Stage #3: ethyl (2R, 3S)-3-(methoxymethyloxy)-2-methylbutanoate In tetrahydrofuran; hexane at 0℃; for 0.25h;	88%

2-(4'-aminophenyl)-4-quinolinecarboxylic acid (94205-62-6) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → 2-{4-[N'-(1-ethyl-2-oxo-propylidene)-hydrazino]-phenyl}-quinoline-4-carboxylic acid

Conditions	Yield
Stage #1: 2-(4'-aminophenyl)-4-quinolinecarboxylic acid Stage #2: ethyl 2-ethyl-3-oxobutanoate With sodium hydroxide; sodium acetate In ethanol; water pH=4 - 4.5; Japp-Klingemann reaction;	87%

aniline (62-53-3) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → C14H19NO2

Conditions	Yield
ammonium cerium(IV) nitrate In ethanol at 20℃; for 3h;	87%

3-bromo-4-chloroaniline (823-54-1) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl (E)-2-(2-(3-bromo-4-chlorophenyl)hydrazineylidene)butanoate

Conditions	Yield
Stage #1: 3-bromo-4-chloroaniline With hydrogenchloride; acetic acid; sodium nitrite In water at 0℃; for 1.16667h; Stage #2: ethyl 2-ethyl-3-oxobutanoate With potassium hydroxide In ethanol; water at 0 - 80℃; for 5h; pH=7;	87%
Stage #1: 3-bromo-4-chloroaniline With hydrogenchloride; acetic acid; sodium nitrite In water at 0℃; for 0.666667h; Stage #2: ethyl 2-ethyl-3-oxobutanoate With potassium hydroxide In ethanol; water at 0 - 80℃; for 5h; pH=7;	87%

ethyl 2-ethyl-3-oxobutanoate (607-97-6) + trimethyl orthoformate (149-73-5) → ethyl 2-ethyl-3,3-dimethoxybutyrate

Conditions	Yield
With toluene-4-sulfonic acid In methanol for 24h; Ambient temperature;	86%

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-ethyl-2-iodo-3-oxobutanoate

Conditions	Yield
With N-iodo-succinimide; magnesium(II) perchlorate In acetonitrile at 20℃; for 0.25h;	86%
With bis(acetylacetonate)oxovanadium; dihydrogen peroxide; sodium iodide In water; ethyl acetate at 0 - 5℃; for 13h; regioselective reaction;	79%

6-amino-4,7-dimethylcoumarin (29001-25-0) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-[2-(4,7-dimethyl-2-oxo-2H-chromen-6-yl)azo]-3-oxo-2-ethyl-butanoate

Conditions	Yield
Stage #1: 6-amino-4,7-dimethylcoumarin With hydrogenchloride; acetic acid; sodium nitrite at 5℃; for 2h; Stage #2: ethyl 2-ethyl-3-oxobutanoate With sodium acetate; acetic acid at 20℃; for 10h; pH=5.5;	86%

N-(2-fluoro-3-nitrophenyl)-4-[(2S)-tetrahydrofuran-2-ylmethoxy]benzamide (1314129-13-9) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl (2E)-2-{[2-fluoro-3-({4-[(2S)-tetrahydrofuran-2-ylmethoxy]benzoyl}amino)phenyl]hydrazono}butanoate (1314129-15-1)

Conditions	Yield
Stage #1: N-(2-fluoro-3-nitrophenyl)-4-[(2S)-tetrahydrofuran-2-ylmethoxy]benzamide With hydrogen; palladium-on-charcoal In tetrahydrofuran; water at 20℃; for 15h; Stage #2: With hydrogenchloride; sodium nitrite In water; acetonitrile at -25 - 5℃; for 0.5h; Stage #3: ethyl 2-ethyl-3-oxobutanoate With potassium hydroxide In water at -20℃;	86%

methyl vinyl ketone (78-94-4) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-ethyl-3-oxo-2-(3-oxo-1-butyl)-butanoate (100315-75-1)

Conditions	Yield
lithium hydroxide In 1,2-dimethoxyethane for 0.5h; Ambient temperature;	85%
lithium iodide In 1,4-dioxane for 12h; Heating;	82%
K bis(1,2-benzenediolato)phenylsilicate In chloroform at 40℃; for 6h; organosilicate-catalyzed Michael addition;	74%
With molecular sieve; Eu(tfc)3 In tetrachloromethane at -33℃; for 72h;	71%
With sodium perchlorate In methanol at 24.84℃; Michael Addition; Electrochemical reaction;

ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-ethyl-2-chloro-3,3-difluorobutyrate (114745-67-4)

Conditions	Yield
With sulfur tetrafluoride; hydrogen fluoride; chlorine at 25℃; for 10h; autoclave;	85%

formaldehyd (50-00-0) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 2-methylenebutyrate (3070-65-3)

Conditions	Yield
Stage #1: ethyl 2-ethyl-3-oxobutanoate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 0.5h; Stage #2: formaldehyd In tetrahydrofuran at -78 - 20℃; Further stages.;	85%

N,N-bis(ethoxymethyl)benzylamine (55686-29-8) + ethyl 2-ethyl-3-oxobutanoate (607-97-6) → ethyl 1-benzyl-3-ethyl-4-oxo-3-piperidinecarboxylate (113385-99-2)

Conditions	Yield
With Methyltrichlorosilane In acetonitrile at 20℃; for 20h; Mannich reaction;	85%

Upstream product

• 857819-83-1 4-ethyl-3-methyl-pentenedioic acid diethyl ester 
• 90833-10-6 2-acetyl-3-methyl-succinic acid-1-ethyl ester 
• 74-96-4 ethyl bromide 
• 141-97-9 ethyl acetoacetate 
• 64-67-5 diethyl sulfate 
• 64-17-5 ethanol 
• 75-03-6 ethyl iodide 
• 141-52-6 sodium ethanolate 
• 105-53-3 diethyl malonate 
• 1007476-32-5 sodium ethyl acetylacetate enolate 
• 141-78-6 ethyl acetate 
• 533-68-6 2-bromobutyric acid ethyl ester 
• 463-51-4 Ketene 
• 66279-50-3 acetoacetic acid ethyl ester; potassium (Z)-enolate 

Downstream Products

• 39083-15-3 5-ethyl-6-methyl-2-thioxo-2,3-dihydropyrimidin-4(1H)-one 
• 152494-54-7 4-ethyl-5-methyl-2-phenyl-1,2-dihydro-pyrazol-3-one 
• 55996-09-3 5-ethyl-2-methoxy-6-methyl-3H-pyrimidin-4-one 
• 106531-84-4 3,4-Dimethyl-1-(6-methyl-benzothiazol-2-yl)-1H-pyrano[2,3-c]pyrazol-6-one 
• 87745-91-3 Ethyl 2-methyl-3-ethyl-4-oxo-4H-pyrido<1,2-a>pyrimidine-7-carboxylate hydrochloride 
• 106515-43-9 1-(6-Methoxy-benzothiazol-2-yl)-3,4-dimethyl-1H-pyrano[2,3-c]pyrazol-6-one 
• 128672-37-7 (Z)-Ethyl 2-Oxobutyrate 2-(2,4-Dichlorophenyl)hydrazone 
• 128692-22-8 (E)-Ethyl 2-Oxobutyrate 2-(2,4-Dichlorophenyl)hydrazone 
• 98189-85-6 7-Ethyl-6-methyl-2,3-diphenyl-7H,9H-imidazo[1,2-b][1,2,4]triazepin-8-one 
• 22287-11-2 3-ethyl-4-methyl-3-penten-2-one 
• 247098-17-5 ethyl-α-ethylacetoacetate cyanohydrin 
• 58120-93-7 pentane-2,3-dione-3-phenylhydrazone 
• 90251-33-5 Pentane-2,3-dione 3-(p-tolylhydrazone) 
• 140139-75-9 3-[(4-Methoxy-phenyl)-hydrazono]-pentan-2-one 

Relevant articles and documents

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Preparation method of remdesivir intermediate 2-ethyl-1-butanol

The invention relates to a preparation method of a remdesivir intermediate 2-ethyl-1-butanol. The preparation method comprises a step of substitution reaction, namely a step of carrying out a substitution reaction on alkyl acetoacetate and halogenated ethane under an alkaline condition to obtain alkyl 2-ethyl-3-oxo-butyrate; a step of addition reduction, namely a step of carrying out an addition reduction reaction on the alkyl 2-ethyl-3-oxo-butyate to obtain alkyl 2-ethylbutyrate; a step of reduction, namely a step of subjecting the alkyl 2-ethylbutyrate to a reduction reaction to prepare 2-ethyl-1-butanol (I). According to the preparation method of the remdesivir intermediate 2-ethyl-1-butanol, the alkyl acetoacetate and halogenated ethane serve as main raw materials, the raw materials are simple and easy to obtain, the 2-ethyl-1-butanol (I) is prepared through substitution reaction, addition reduction and reduction reaction, the process is simple, economical and environmentally friendly, the product is convenient to obtain, and industrial production of remdesivir bulk drugs is facilitated.

Substituted quinolinone inhibitor

The invention provides a substituted quinolinone inhibitor and relates to a compound as shown in a formula (II) which is described in the specification or a pharmaceutically acceptable salt, solvate,active metabolite, polymorphic substance, ester, isomer or prodrug thereof, a pharmaceutical composition containing the compound as shown in the formula (II), and application of the compound and the pharmaceutical composition to treatment of diseases related to abnormal TOPK activity.

Highly crystalline poly(heptazine imides) by mechanochemical synthesis for photooxidation of various organic substrates using an intriguing electron acceptor – Elemental sulfur

Low-defect potassium poly(heptazine imide) (PHIK-BM) was engineered for application in photocatalytic oxidation of organic substrates. Mechanochemical pretreatment of a mixture of 5-aminotetrazole in LiCl/KCl eutectics using high-energy ball milling afforded a highly homogeneous mixture that, upon sequential thermolysis at 600?°C, gave nanosized particles of PHIK–BM. The photocatalytic activity of the free-standing PHIK–BM plates was assessed in the oxidation of benzyl alcohol to benzaldehyde under visible light irradiation using elemental sulfur as an electron acceptor. Both quantitative conversion (>99%) of benzyl alcohol and selectivity (>98%) with respect to benzaldehyde were achieved. The developed method was extended to aliphatic alcohol oxidation coupled with multicomponent Hantzsch 1,4-dihydropyridine synthesis. These 1,4-dihydropyridines were also photocatalytically oxidized by PHIK–BM to the corresponding substituted pyridines, with very good yields and under mild metal-free conditions.