638-07-3

Basic information

• Product Name: Ethyl 4-chloroacetoacetate
• Synonyms: AKOS BBS-00004336;4-CHLOROACETOACETIC ACID ETHYL ESTER;BUTANOIC ACID, 4-CHLORO-3-OXO-ETHYL ESTER;ETHYL 4-CHLOROACETOACETATE;ETHYL 4-CHLORO-3-OXOBUTANOATE;ETHYL-GAMMA-CHLOROACETOACETATE;4-chloro-3-oxo-butanoicaciethylester;4-chloro-acetoaceticaciethylester
• CAS NO: 638-07-3
• Molecular Formula: C₆H₉ClO₃
• Molecular Weight: 164.59
• EINECS: 211-317-0
• Product Categories: Pharmaceutical Intermediates;Halogen compounds;C6 to C7;Carbonyl Compounds;Esters;Aliphatics
• Mol File: 638-07-3.mol

Chemical Properties

• Melting Point: -8 °C
• Boiling Point: 115 °C14 mm Hg(lit.)
• Flash Point: 206 °F
• Appearance: Clear colorless to pale reddish-yellow/Liquid
• Density: 1.218 g/mL at 25 °C(lit.)
• Vapor Pressure: 2.87E-05mmHg at 25°C
• Refractive Index: n20/D 1.452(lit.)
• Storage Temp.: 2-8°C
• Solubility: 47.0g/l
• PKA: 9.56±0.46(Predicted)
• Explosive Limit: 1.8%(V)
• Water Solubility: 47.5 g/L (20 ºC)
• BRN: 1761275
• CAS DataBase Reference: Ethyl 4-chloroacetoacetate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl 4-chloroacetoacetate(638-07-3)
• EPA Substance Registry System: Ethyl 4-chloroacetoacetate(638-07-3)

Safety Data

• Hazard Codes: T,N,C
• Statements: 25-34-51/53-24/25-36
• Safety Statements: 26-36-45-61-36/37/39-27
• RIDADR: UN 2922 8/PG 2
• WGK Germany: 3
• RTECS: AK5110000
• F: 8-10-19-21
• TSCA: Yes
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 638-07-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl 4-chloroacetoacetate is used as an intermediate in the synthesis of various pharmaceutical compounds, such as ethyl 4-chloro-3-arylaminocrotonates, diethyl succinylsuccinate, 2-alkyl-4-hydroxy-6-chloromethylpyrimidines, and 4-chloromethylcoumarines. Its reactivity and functional groups make it a valuable component in the development of new drugs and medications.
Used in Film Coating Industry:
Ethyl 4-chloroacetoacetate is used as a precursor in the preparation of phosphorous ylides, which are essential in the production of regular film coatings. These coatings are applied to various surfaces to provide protection, enhance appearance, and improve durability.
Used in Pharmaceutical Coating:
In the pharmaceutical industry, Ethyl 4-chloroacetoacetate is also used in the development of pharmaceutical coatings. These coatings can improve the stability, bioavailability, and controlled release of active pharmaceutical ingredients, ensuring optimal drug delivery and effectiveness.
Overall, Ethyl 4-chloroacetoacetate is a crucial compound in the synthesis of various pharmaceuticals, film coatings, and other applications, making it an essential component in the chemical and pharmaceutical industries.

InChI:InChI=1/C9H13NO2/c1-2-7-3-4-8(10-5-7)9(12)6-11/h3-5,9,11-12H,2,6H2,1H3

Synthetic route

ethyl acetoacetate (141-97-9) → ethyl (2-chloroaceto)acetate (638-07-3)

Conditions	Yield
Stage #1: ethyl acetoacetate With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at 0℃; for 1h; Inert atmosphere; Stage #2: With methyl chlorosulfate In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere;	100%

ethyl acetate (141-78-6) + chloroacetic acid ethyl ester (105-39-5) → ethyl (2-chloroaceto)acetate (638-07-3)

Conditions	Yield
In ethanol; dimethyl sulfoxide at 128 - 152℃; under 3648.24 - 6840.46 Torr; for 22h; Temperature; Pressure; Inert atmosphere;	98.7%

ethyl acetate (141-78-6) + methyl chloroacetate (96-34-4) → ethyl (2-chloroaceto)acetate (638-07-3)

Conditions	Yield
In methanol; N,N-dimethyl-formamide at 110 - 145℃; under 2280.15 - 6080.41 Torr; for 15h; Inert atmosphere;	97.3%

4-methyleneoxetan-2-one (674-82-8) + ethanol (64-17-5) → ethyl (2-chloroaceto)acetate (638-07-3)

Conditions	Yield
Stage #1: 4-methyleneoxetan-2-one With chlorine In dichloromethane under 225.023 Torr; Flow reactor; Stage #2: ethanol at 40 - 70℃; under 712.571 Torr; for 4h;	93%
Stage #1: 4-methyleneoxetan-2-one With chlorine; sodium hydroxide; copper dichloride In dichloromethane at -40 - 10℃; Stage #2: ethanol In dichloromethane Temperature;	90%

n-hexan-2-one (591-78-6) + 4,4-dichloro-3-oxobutyric acid ethyl ester (6082-74-2) → ethyl (2-chloroaceto)acetate (638-07-3) + (Z)-5-Methyl-3-oxo-non-4-enoic acid ethyl ester

Conditions	Yield
With iron pentacarbonyl In benzene at 80℃; Reformatsky-type addition;	A 75 % Chromat. B n/a

n-hexan-2-one (591-78-6) + 4,4-dichloro-3-oxobutyric acid ethyl ester (6082-74-2) → ethyl (2-chloroaceto)acetate (638-07-3) + ethyl acetoacetate (141-97-9)

Conditions	Yield
With iron pentacarbonyl; water; N,N-dimethyl-formamide In benzene at 80℃;	A 40 % Chromat. B 16 % Chromat.

4,4-dichloro-3-oxobutyric acid ethyl ester (6082-74-2) → ethyl (2-chloroaceto)acetate (638-07-3)

Conditions	Yield
With iron pentacarbonyl; water In benzene at 80℃;	65 % Chromat.

4,4-dichloro-3-oxobutyric acid ethyl ester (6082-74-2) + benzaldehyde (100-52-7) → ethyl (2-chloroaceto)acetate (638-07-3) + ethyl 3-oxo-5-phenylpent-4-enoate (1503-99-7)

Conditions	Yield
With iron pentacarbonyl In benzene at 80℃; Reformatsky-type addition;	A 70 % Chromat. B n/a

4-chloroacetoacetyl chloride (41295-64-1) + ethanol (64-17-5) → ethyl (2-chloroaceto)acetate (638-07-3)

Conditions	Yield
Stage #1: 4-chloroacetoacetyl chloride; ethanol Industry scale; Stage #2: With sodium hydroxide In water Product distribution / selectivity;
In dichloromethane	156.3 g

O-methylresorcine (150-19-6) + ethyl (2-chloroaceto)acetate (638-07-3) → 4-(chloromethyl)-7-methoxy-2H-chromen-2-one (41295-55-0)

Conditions	Yield
With methanesulfonic acid at 20℃;	100%
With silica gel supported zirconyl chloride octahydrate at 90℃; for 0.5h; Pechmann condensation reaction;	96%
With perchloric acid; sulfuric acid at 25℃;	95.2%

ethyl (2-chloroaceto)acetate (638-07-3) + 2-mercaptoacetophenone (2462-02-4) → 3-Oxo-4-(2-oxo-2-phenyl-ethylsulfanyl)-butyric acid ethyl ester (114250-85-0)

Conditions	Yield
With potassium carbonate In tetrahydrofuran	100%

ethyl (2-chloroaceto)acetate (638-07-3) + 4-fluorothiobenzamide (22179-72-2) → ethyl 2-(2-(4-fluorophenyl)thiazol-4-yl)acetate (78742-98-0)

Conditions	Yield
In ethanol for 4h; Heating;	100%
In ethanol for 5h; Reflux; Inert atmosphere;	89%
In ethanol for 7.5h; Reflux;	89%

ethyl (2-chloroaceto)acetate (638-07-3) + 3-chloro-4-methoxybenzenethiol (89818-37-1) → ethyl 4-(3'-chloro-4'-methoxyphenylthio)acetoacetate (89818-38-2)

Conditions	Yield
In pyridine; diethyl ether for 2h; Heating;	100%

ethyl (2-chloroaceto)acetate (638-07-3) → ethyl (S)-4-chloro-3-hydroxybutanoate (10488-69-4, 86728-85-0, 87068-18-6, 90866-33-4)

Conditions	Yield
With formic acid; NAD; sodium formate; formate dehydrogenase In water at 30℃; for 3.5h; pH=6.5;	100%
With Escherichia coli BL21 (fdh, adh)-cells In water for 1h; pH=6.5;	99.3%
With hydrogen; (R)-[RuCl2(BINAP)]n In ethanol at 95 - 105℃; under 67506.8 - 75007.5 Torr; for 0.5 - 8h; Conversion of starting material;	98%

ethyl (2-chloroaceto)acetate (638-07-3) + cyclohexanol (108-93-0) → 4-(Cyclohexyloxy)acetessigsaeure-ethylester (126930-22-1)

Conditions	Yield
Stage #1: cyclohexanol With sodium hydride In diethyl ether at 20℃; for 1.25h; Stage #2: ethyl (2-chloroaceto)acetate In diethyl ether at 20℃;	100%
With sodium hydride 1.) ether, 2 h, RT; 2.) 20 h, RT; Yield given. Multistep reaction;

pyridine (110-86-1) + ethyl (2-chloroaceto)acetate (638-07-3) → 1-(ethoxycarbonylacetonyl)pyridinium chloride

Conditions	Yield
at 20℃; for 24h;	100%

picoline (108-89-4) + ethyl (2-chloroaceto)acetate (638-07-3) → 1-ethoxycarbonylacetonyl-4-methylpyridinium chloride

Conditions	Yield
at 20℃; for 24h;	100%

3,5-Lutidine (591-22-0) + ethyl (2-chloroaceto)acetate (638-07-3) → 1-ethoxycarbonylacetonyl-3,5-dimethylpyridinium chloride

Conditions	Yield
at 20℃; for 24h;	100%

ethyl (2-chloroaceto)acetate (638-07-3) + 4-Bromoresorcinol (6626-15-9) → 6-bromo-4-(chloromethyl)-7-hydroxy-2H-chromen-2-one (223420-33-5)

Conditions	Yield
In methanesulfonic acid at 25℃; for 2h;	100%
With methanesulfonic acid at 20℃; for 2h; Inert atmosphere; Darkness;	91%
With sulfuric acid Inert atmosphere;	88%

ethyl (2-chloroaceto)acetate (638-07-3) + 3,3-diphenylpropan-1-ol (20017-67-8) → (3,3-diphenylpropane-1-yl) 4-chloroacetoacetate (314776-40-4)

Conditions	Yield
In toluene at 130℃;	100%
In toluene

ethyl (2-chloroaceto)acetate (638-07-3) + 2,4-dichlorobenzaldeyhde (874-42-0) → (Z)-ethyl 4-chloro-2-(2,4-dichlorobenzylidene)-3-oxobutanoate (915296-79-6)

Conditions	Yield
With acetic acid; benzylamine In isopropyl alcohol at 20℃; for 96h; Knoevenagel Condensation; Inert atmosphere;	100%
With acetic acid; benzylamine In isopropyl alcohol at 20℃; for 96h;
With acetic acid; benzylamine In isopropyl alcohol at 20℃; for 96h;

5-bromo-2-pyridylamine (1072-97-5) + ethyl (2-chloroaceto)acetate (638-07-3) → ethyl 2-(6-bromoimidazo[1,2-a]pyridin-2-yl)acetate (59128-04-0)

Conditions	Yield
In ethanol for 4h; Reflux; Inert atmosphere;	100%
In toluene Reflux;	24%
In toluene at 115℃; for 18h;
In ethanol Heating / reflux;

morpholinothiourea (14294-10-1) + ethyl (2-chloroaceto)acetate (638-07-3) → ethyl (2-morpholin-4-yl-1,3-thiazol-4-yl)acetate (329906-01-6)

Conditions	Yield
With triethylamine In ethanol at 80℃; for 3h;	100%
Stage #1: morpholinothiourea; ethyl (2-chloroaceto)acetate In ethanol at 80℃; for 3h; Stage #2: With water; sodium hydrogencarbonate	100%

morpholine-4-carboxylic acid amide (2158-02-3) + ethyl (2-chloroaceto)acetate (638-07-3) → ethyl (2-morpholin-4-yl-1,3-thiazol-4-yl)acetate (329906-01-6)

Conditions	Yield
In ethanol at 80℃; for 3h;	100%

ethyl (2-chloroaceto)acetate (638-07-3) + phosphonic acid diethyl ester (762-04-9) → ethyl 4-diethoxyphosphoryl-3-oxobutanoate (65043-08-5)

Conditions	Yield
With sodium hydride	100%

ethyl (2-chloroaceto)acetate (638-07-3) + 2-amino-5-chloro-3-hydroxypyridine (40966-87-8) → 7-chloro-2-(chloromethyl)-9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one

Conditions	Yield
With phosphoric acid at 110℃; for 2.5h;	100%

ethyl (2-chloroaceto)acetate (638-07-3) + 4,6-dimethyl-2-meraptopyrimidine (22325-27-5) → ethyl 4-[(4,6-dimethylpyrimidin-2-yl)sulfanyl]-3-oxobutanoate

Conditions	Yield
With triethylamine at 0℃; for 0.5h; Reagent/catalyst; Temperature;	100%

ethyl (2-chloroaceto)acetate (638-07-3) → ethyl (L)-4-chloro-3-hydroxybutyrate (10488-69-4, 86728-85-0, 87068-18-6, 90866-33-4)

Conditions	Yield
With D-glucose; β-keto ester reductase L-1; tris hydrochloride; NADPH at 30℃; for 48h; relative reaction rate; other β-keto esters; var. time;	99%
With D-glucose; tris hydrochloride at 30℃; for 48h; β-keto ester reductase L-1, NADPH, GDH;	99%
With D-glucose; YOL151W reductase In aq. phosphate buffer; toluene pH=6.7; Enzymatic reaction;	98.7%

3,5-dihydroxyphenol (108-73-6) + ethyl (2-chloroaceto)acetate (638-07-3) → 4-chloromethyl-5,7-dihydroxy-chromen-2-one (809234-33-1)

Conditions	Yield
With methanesulfonic acid at 20℃; for 6h;	99%
With silica gel supported zirconyl chloride octahydrate at 90℃; for 0.0833333h; Pechmann condensation reaction;	98%
With yttrium(lll) nitrate hexahydrate at 90℃; for 0.2h; Pechmann Condensation; Green chemistry;	98%

ethyl (2-chloroaceto)acetate (638-07-3) + α-naphthol (90-15-3) → 4-(chloromethyl)-2H-benzo[h]chromen-2-one

Conditions	Yield
With silica gel supported zirconyl chloride octahydrate at 90℃; for 0.75h; Pechmann condensation reaction;	99%
With sulfuric acid; silica gel at 80℃; for 1h; Pechmann condensation reaction;	96%
With ammonium cerium(IV) nitrate; silica gel for 0.05h; Pechmann reaction; microwave irradiation;	96%

ethyl (2-chloroaceto)acetate (638-07-3) + 3-methoxybenzenethiol (15570-12-4) → 3-methoxybenzenethiol (16768-98-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 0 - 20℃; for 2h;	99%
With potassium hydroxide In methanol at 20℃; for 6h;
With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20℃; for 2.16667h;

2-aminopyridine (504-29-0) + ethyl (2-chloroaceto)acetate (638-07-3) → 2-(chloromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (16867-35-9)

Conditions	Yield
With PPA at 120℃; for 2h;	99%
With polyphosphate at 45 - 125℃; for 2h;	67%
In PPA; (2S)-N-methyl-1-phenylpropan-2-amine hydrate
In PPA; (2S)-N-methyl-1-phenylpropan-2-amine hydrate
Stage #1: 2-aminopyridine; ethyl (2-chloroaceto)acetate at 125℃; for 5h; Stage #2: With sodium hydroxide In water pH=6 - 7; Cooling with ice;

ethyl (2-chloroaceto)acetate (638-07-3) → 2-(chloromethyl)-4H-pyrido[1,2-a]pyrimidin-4-one (16867-35-9)

Conditions	Yield
Stage #1: 2-aminopyridine With PPA at 120℃; Stage #2: ethyl (2-chloroaceto)acetate at 120℃; for 2h;	99%

ethyl (2-chloroaceto)acetate (638-07-3) + 4-methyl resorcinol (496-73-1) → 4-(chloromethyl)-7-hydroxy-6-methyl-2H-chromen-2-one (1239755-10-2)

Conditions	Yield
Stage #1: ethyl (2-chloroaceto)acetate With sulfuric acid at 0℃; Stage #2: 4-methyl resorcinol at 20℃;	99%
With sulfuric acid at 0 - 20℃;	99%
With sulfuric acid at 0 - 20℃; for 24h; Pechmann Condensation;	73%

ethyl (2-chloroaceto)acetate (638-07-3) + N-butylamine (109-73-9) → N-butyl-2-chloroacetamide (5349-24-6)

Conditions	Yield
With 4-toluenesulfonyl azide In tetrahydrofuran at 20 - 25℃;	99%

ethyl (2-chloroaceto)acetate (638-07-3) + anthranilic acid amide (28144-70-9) → 2-(chloromethyl)quinazolin-4(3H)-one (3817-05-8)

Conditions	Yield
With ethanolamine-phosphoric acid functionalized polyacrylonitrile fibers (PANEAPF) In water at 100℃; for 15h; Green chemistry;	99%

ethyl (2-chloroaceto)acetate (638-07-3) + 2-hydroxyresorcinol (87-66-1) → 4-chloromethyl-7,8-dihydroxy<1>benzopyran-2(H)-one (19040-71-2)

Conditions	Yield
zirconium(IV) chloride at 20℃; for 0.0833333h;	98%
With ammonium cerium(IV) nitrate; silica gel for 0.0333333h; Pechmann reaction; microwave irradiation;	96%
With bispyridine cobalt(II) chloride for 0.05h; Pechmann condensation; Microwave irradiation; neat (no solvent);	95%

Upstream product

• 591-78-6 n-hexan-2-one 
• 6082-74-2 4,4-dichloro-3-oxobutyric acid ethyl ester 
• 100-52-7 benzaldehyde 
• 141-97-9 ethyl acetoacetate 
• 141-78-6 ethyl acetate 
• 105-39-5 chloroacetic acid ethyl ester 
• 96-34-4 methyl chloroacetate 
• 674-82-8 4-methyleneoxetan-2-one 
• 64-17-5 ethanol 
• 41295-64-1 4-chloroacetoacetyl chloride 

Downstream Products

• 82617-90-1 2-chloroacetyl-3-phenyl-acrylic acid ethyl ester 
• 1131-09-5 benzo[b]thiophene-3-acetic acid 
• 38449-49-9 2-mercapto-4-ethoxycarbonylmethylthiazole 
• 37128-24-8 ethyl (2-methyl-1,3-thiazol-4-yl)acetate 
• 84691-16-7 ethyl 4-hydroxy-1,2-oxazole-3-carboxylate 
• 62773-09-5 7-chloromethyl-5H-thiazolo<3,2-a>pyrimidin-5-one 
• 62773-11-9 2-Chlormethyl-4H-pyrimido<2,1-b>benzothiazol-4-on 
• 20485-39-6 ethyl 4-methyloxazole-5-carboxylate 
• 16807-31-1 γ-(3,4,5-Trimethoxy-phenylmercapto)-acetessigethylester 
• 37072-41-6 ethyl 2-benzylidenehydrazonothiazole-4-acetate 
• 66870-61-9 ethyl 2-(2-benzoylhydrazino)thiazole-4-acetate 
• 38449-49-9 2-mercapto-thiazole-4-acetic acid,ethyl ester 
• 73217-06-8 (2-amino-4-oxo-3,5-dihydro-4H-pyrimido[4,5-b][1,4]oxazin-6-ylidene)-acetic acid ethyl ester 
• 72195-13-2 2a-hydroxy-2a,3-dihydro-2H,5H-1-thia-5,8,8b-triaza-acenaphthylene-4,7-dione 

Relevant articles and documents

Preparation method of ethyl 4-chloroacetoacetate

The invention discloses a preparation method of ethyl 4-chloroacetoacetate, which specifically comprises the following steps of: (1) chlorination: cooling dichloromethane for the first time, then adding acetyl ketene for cooling for the second time, then introducing chlorine gas, and keeping the temperature; (2) esterification: dropwise adding absolute ethyl alcohol, and keeping the temperature; (3) desolvation and deacidification: heating and distilling to remove dichloromethane and hydrogen chloride; and (4) rectification: rectifying and purifying to obtain the product. Acetyl ketene is used as a raw material, the raw material is low in cost and easy to obtain, the synthesis steps are simple, and the production cost is reduced; by optimizing the ratio of process materials, the selectivity of the product ethyl 4-chloroacetoacetate is improved, and the yield is increased; and through high-vacuum low-temperature distillation, the decomposition of the heat-sensitive product ethyl 4-chloroacetoacetate is effectively prevented, and the yield and the product quality are improved.

Continuous device and method for industrial production 4 - chloroacetoacetate

The invention relates to an industrial production 4 - chloroacetoacetate continuous device and a method. The device and method can inhibit the generation of byproduct 2 - chloroacetoacetate and 4 - chloroacetoacetate in 2 - chloroacetoacetate crude product can be controlled below 0.15%. The yield of 4 - chloroacetoacetate can be improved, and the yield 4 - chloroacetoacetate can reach 97% or more. The continuous device and the method provided by the invention can be operated continuously, 4 - chloroacetoacetate can be industrially produced, and the continuous device has remarkable economic value.

Synthetic method for ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate

The invention discloses a synthetic method for ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate. The method is characterized by comprising the following steps: a, performing chlorination on diketene, and performing alcoholysis to synthesize ethyl 4-chloroacetoacetate; b, performing oximation on the ethyl 4-chloroacetoacetate to synthesize ethyl 4-chloro-2-(hydroxyimino)-3-oxobutanoate; c, performing a reaction on the ethyl 4-chloro-2-(hydroxyimino)-3-oxobutanoate and thiourea to synthesize ethyl 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetate; and d, performing hydrocarbonylation on the ethyl2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetate to synthesize the ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate. The method has the following advantages: 1, the chlorination reaction in the stepa is a continuous reaction, and has a fast reaction speed and no accumulation of a large amount of dangerous materials, so that the danger is small; 2, the costs of equipment are lower, the equipmentis conventional organic synthesis equipment, no expensive and special equipment is needed, so that the equipment is easy to copy, and the production efficiency is improved; and 3, the diketene is directly used as a raw material, the raw material cost is low, the synthetic steps are simple to operate, so that the method facilitates reducing the production costs of the ethyl 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate.

Method for preparing 4-chloracetylethyl acetoacetate

The invention relates to a method for preparing 4-chloracetylethyl acetoacetate. The method comprises the steps: adding ketene dimer into a dichloromethane (DCM) solvent with a temperature of -40 DEGC to -20 DEG C, adding alkaline substances, carrying out uniform stirring, keeping a temperature of a solution system to be -40 DEG C to -20 DEG C, and introducing chlorine gas into the solution withstirring; and after the reaction is completed, adjusting the temperature of the solution to be -40 DEG C to -10 DEG C, dropwise adding ethanol into the solution, carrying out stirring until the reaction is full, and subjecting a product to distillation and rectification, thereby obtaining a target product, i.e., the 4-chloracetylethyl acetoacetate. According to the preparation method disclosed bythe invention, the proportion of a product 1 in a chlorination reaction can be increased, and then, the yield of the final 4-chloracetylethyl acetoacetate is increased.

Method for synthesizing oxiracetam intermediate 4-ethyl chloroacetoacetate

The invention discloses a method for synthesizing oxiracetam intermediate 4-ethyl chloroacetoacetate and belongs to the field of pharmacy. The method is characterized in that chloroacetate and ethyl acetate react under the action of a catalyst to obtain the 4-ethyl chloroacetoacetate. The reaction process is: (1) evenly mixing the ethyl acetate, the catalyst and a solvent A, introducing protectivegas, controlling the pressure to be 0.3-0.5 Mpa, controlling the temperature to be 110-135 DEG C, adding a solution prepared from chloroacetate and a solvent B dropwise, controlling the addition timeto be 15-25 min, after chloroacetate and the solvent B are added, increasing the reaction temperature to 145-160 DEG C, increasing the pressure to 0.8-1 Mpa, continuing the reaction for 15-25 h, andthen ending the reaction; and (2) after a system is cooled, filtering the system to remove solid, adding filtrate to water with the volume being 3-5 times that of the filtrate, using a solvent C for extraction, and after an extract is dried with a drying agent, concentrating and evaporating the solvents to obtain a product. The method for synthesizing the oxiracetam intermediate 4-ethyl chloroacetoacetate has the advantages of relatively short steps, low process cost and few side effects.

Efficient α-chlorination of carbonyl containing compounds under basic conditions using methyl chlorosulfate

An efficient method for the α-chlorination of ketones under basic conditions is described using methyl chlorosulfate. Its applicability for the chlorination of other functional groups has also been studied and it is equally useful for the synthesis of α-chloroesters and amides. Methyl chlorosulfate is described for the first time as a positive chlorine source. Some aldol reactions which occur during the chlorination of some substrates are also reported.

A 4-chloro-acetyl-acetic acid ethyl ester preparation method

The invention relates to a preparation method of 4-chloracetyl ethyl acetate. The preparation method comprises the following steps: by taking diketene as an initial raw material, synthesizing a 4-chloracetyl ethyl acetate coarse product in two steps: chlorination and esterification; then, rectifying to obtain a finished product, and adding a stabilizer anhydrous cupric sulfate into the chlorination step, wherein the addition is 0.02-1wt% of diketene. Compared with the prior art, the preparation method provided by the invention has the advantages that 1, by adding the stabilizer anhydrous cupric sulfate, the production of a byproduct 2-chloracetyl ethyl acetate is reduced and the production of the byproduct 2-chloracetyl ethyl acetate in the 4-chloracetyl ethyl acetate coarse product can be controlled below 0.5%, so that the distill yield is greatly improved; 2, the yield of 2-chloracetyl ethyl acetate is over 94.5%, and the cost is greatly lowered.

Process for the production of 4-chloroacetyl chloride, 4-chloroacetic acid esters, amides and imides

The invention relates to process for the continuous production of 4-chloroacetoacetyl chloride, comprising the steps of (a) feeding diketene and chlorine into a thin film reactor and (b) reacting the diketene and chlorine to obtain 4-chloroacetoacetyl chloride. The invention also relates to a process for the production of 4-chloroacetic acid ester, 4-chloroacetic acid amide or 4-chloroacetic acid imide from 4-chloroacetoacetyl chloride obtained according to the inventive process.

Reactions of diethyl dibromomalonate and ethyl 2,2-dichloroacetoacetate with water and carbonyl compounds (aldehydes and ketones) in the presence of pentacarbonyliron

Diethyl dibromomalonate and ethyl 2,2-dichloroacetoacetate are effectively reduced with the system pentacarbonyliron-proton-donor compound (water or butyl methyl ketone) to give the corresponding hydrodehalogenation products. These results provide a support for the previous assumption that the key reaction stage is reduction with pentacarbonyliron of initially formed radical to anion which is then involved in proton transfer.

Method for preparing chiral diphosphines

The invention concerns a method for preparing a compound of formula (1) wherein: A represents naphthyl or phenyl optionally substituted; and Ar1, Ar2independently represent a saturated or aromatic carbocyclic group, optionally substituted.