37517-81-0

Basic information

• Product Name: Methyl malonyl chloride
• Synonyms: METHYL 3-CHLORO-3-OXOPROPIONATE;METHYL MALONYL CHLORIDE;METHYL CHLOROFORMYLACETATE;AURORA KA-3053;Propanoic acid, 3-chloro-3-oxo-, methyl ester;Malonic acid monomethyl ester chloride~Methyl (chloroformyl)acetate;Mehtyl Malonyl Chloride;METHYL 3-CHLORO-3-OXOPROPIONATE,97%
• CAS NO: 37517-81-0
• Molecular Formula: C₄H₅ClO₃
• Molecular Weight: 136.53
• EINECS: 253-540-6
• Product Categories: Acid Halides;Building Blocks;Carbonyl Compounds;Chemical Synthesis;Organic Building Blocks
• Mol File: 37517-81-0.mol
• Article Data: 13

Chemical Properties

• Boiling Point: 57-59 °C12 mm Hg(lit.)
• Flash Point: 176 °F
• Appearance: Colorless/Liquid
• Density: 1.273 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.69mmHg at 25°C
• Refractive Index: n20/D 1.432(lit.)
• Storage Temp.: 2-8°C
• PKA: 9.33±0.46(Predicted)
• Water Solubility: Reacts with water.
• Sensitive: Lachrymatory
• BRN: 1754078
• CAS DataBase Reference: Methyl malonyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl malonyl chloride(37517-81-0)
• EPA Substance Registry System: Methyl malonyl chloride(37517-81-0)

Safety Data

• Hazard Codes: C
• Statements: 34-36/37
• Safety Statements: 26-36/37/39-45
• RIDADR: UN 3265 8/PG 2
• WGK Germany: 3
• F: 8-10-19
• HazardClass: 8
• PackingGroup: II
• Hazardous Substances Data: 37517-81-0(Hazardous Substances Data)

Usage

Chemical Properties

Clear light yellow to yellow liquid

Uses

Methyl malonyl chloride is used as pharmaceutical intermediate. Used in anti-cancer drugs.

General Description

Methyl 3-chloro-3-oxopropionate reacts with 4-cyano-1,1′-biphenyl derivatives bearing ω-hydroxyalkyl substituents to yield liquid-crystalline linear malonates and cyanoacetates.

InChI:InChI=1/C4H5ClO3/c1-8-4(7)2-3(5)6/h2H2,1H3

Synthetic route

Malonic acid monomethyl ester (16695-14-0) → 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0)

Conditions	Yield
With thionyl chloride; N,N-dimethyl-formamide In chloroform Heating;	65%
With phosphorus pentachloride In dichloromethane for 0.5h; Heating;
With thionyl chloride In dichloromethane
Stage #1: Malonic acid monomethyl ester In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.0833333h; Inert atmosphere; Stage #2: With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 20℃; for 2h; Cooling with ice;
With thionyl chloride at 80℃; for 2h; Inert atmosphere;

monomethyl monopotassium malonate (38330-80-2) → 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0)

Conditions	Yield
With oxalyl dichloride In benzene
With thionyl chloride
With thionyl chloride In dichloromethane for 2h; Ambient temperature;
With hexachloroethane; triphenylphosphine In dichloromethane
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 2h; Inert atmosphere;

potassium salt of malonic acid monomethyl ester → 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0)

Conditions	Yield
With thionyl chloride; diethyl ether unter Kuehlung mit Eis-Kochsalz-Gemisch;

methyl 3-({4-[(dimethylamino)carbonyl]phenyl}amino)-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate → 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0)

methyl hydrogen succinate (3878-55-5) → 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0)

Conditions	Yield
With thionyl chloride In benzene for 1.5h; Reflux;

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + aniline (62-53-3) → Methyl 2-(N-phenylaminocarbonyl)acetate (76311-94-9)

Conditions	Yield
In dichloromethane at 0℃; for 1h;	100%
With triethylamine In dichloromethane for 2h; Inert atmosphere;	99%
With triethylamine In dichloromethane at 0 - 20℃; for 5h; Inert atmosphere;	99%

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + N-ethyl-N-phenylamine (103-69-5) → methyl 3-(N-ethyl-N-phenylamino)-3-oxopropionate (142613-14-7)

Conditions	Yield
In dichloromethane at 20℃; for 14h; Inert atmosphere;	100%
With triethylamine In acetone at 2 - 20℃; for 2h; Inert atmosphere;	94%
With pyridine
With triethylamine In tetrahydrofuran at 0 - 20℃; for 2h;

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + 2'-chloro-3,5-dimethyl-2-methylaminobenzophenone (136281-04-4) → methyl N-<2-(2-chlorobenzoyl)-4,6-dimethylphenyl>-N-methylmalonylamide (136281-05-5)

Conditions	Yield
With triethylamine In ethyl acetate for 1.5h;	100%

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + ethanethiol (75-08-1) → methyl 3-ethylthio-3-oxopropanoate

Conditions	Yield
In dichloromethane at 0 - 20℃;	100%
In dichloromethane at 0 - 20℃; for 15h; Inert atmosphere;	100%

4-Chloro-3-nitroaniline (635-22-3) + 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) → N-(4-chloro-3-nitro-phenyl)-malonamic acid methyl ester (852312-59-5)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	100%

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + 4-bromo-aniline (106-40-1) → methyl 3-((4-bromophenyl)amino)-3-oxopropanoate (669000-20-8)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	100%
Stage #1: 4-bromo-aniline With triethylamine In ethyl acetate at 10℃; Stage #2: 3-chloro-3-oxopropanoic acid methyl ester at 17℃; for 0.75h;	122.75 g

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + p-aminoiodobenzene (540-37-4) → methyl 3-((4-iodophenyl)amino)-3-oxopropanoate (658709-61-6)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	100%
With triethylamine In ethyl acetate at 20℃; for 16h; Cooling with acetone-dry ice;	99%
With triethylamine In ethyl acetate at 10 - 15℃; for 0.5h;	29.8 g

4-fluoro-1-(3-methyl-butylamino)-1H-pyrrole-2-carboxylic acid allyl ester (1000313-08-5) + 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) → 1-[(2-methoxycarbonyl-acetyl)-(3-methyl-butyl)-amino]-4-fluoro-1H-pyrrole-2-carboxylic acid allyl ester (1000313-09-6)

Conditions	Yield
In 1,4-dioxane at 100℃; for 1h;	100%

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + methyl 3-amino-3-phenylpropanoate (14898-52-3) → (RS)-(+/-)-N-(2-(methoxycarbonyl)-1-phenylethyl)malonamic acid methyl ester (656808-19-4)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 16h;	100%
With triethylamine In dichloromethane at 20℃; for 2h;

(2S)-2-(1-carboxyethyl)pyrrolidine + 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) → (2S)-1-methylmalonyl-2-(1-carboxyethyl)pyrrolidine (500008-01-5)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 0.75h;	100%

(2S,4S)-4-methoxyhomoproline hydrochloride (500008-09-3) + 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) → (2S,4S)-4-methoxy-1-methylmalonylhomoproline (443984-08-5)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃; for 2.25h;	100%

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + 4-fluoroaniline (371-40-4) → methyl 3-((4-fluorophenyl)amino)-3-oxopropanoate (130112-64-0)

Conditions	Yield
With triethylamine In tetrahydrofuran at 0 - 20℃; for 4h;	100%
With triethylamine In acetone at 20℃; for 5h;	100%
With sodium hydrogencarbonate In acetone at 20℃; for 12h;	94%
In dichloromethane at 20℃; for 8h;
With triethylamine In dichloromethane at 20℃; for 3h;

3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) + cyclohexylamine (108-91-8) → Malonsaeure-methylester-cyclohexylamid (59358-85-9)

Conditions	Yield
In dichloromethane at 0 - 20℃; for 1h;	100%
In dichloromethane at 20℃; for 8h;

(S)-tert-butyl 1-(4-(4-aminophenyl)-5-chloro-1H-imidazol-2-yl)-2-phenylethylcarbamate (942316-85-0) + 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) → (S)-methyl 3-(4-(2-(1-(tert-butoxycarbonylamino)-2-phenylethyl)-5-chloro-1H-imidazol-4-yl)phenylamino)-3-oxopropanoate (942316-86-1)

Conditions	Yield
With triethylamine In dichloromethane at 0℃; for 4h;	100%

2-(2,3,4-trimethoxyphenyl)ethylamine (3937-16-4) + 3-chloro-3-oxopropanoic acid methyl ester (37517-81-0) → N-[2-(2,3,4-trimethoxyphenyl)ethyl]methoxycarbonylacetamide (1176080-20-8)

Conditions	Yield
With potassium carbonate In dichloromethane; water at 0℃; for 1h; Schotten-Baumann reaction;	100%

Upstream product

• 3878-55-5 methyl hydrogen succinate 
• 38330-80-2 monomethyl monopotassium malonate 
• 16695-14-0 Malonic acid monomethyl ester 

Downstream Products

• 27140-28-9 N-{4-[(2-Methoxycarbonyl-acetylamino)-methyl]-benzyl}-malonamic acid methyl ester 
• 142613-15-8 N-Benzyl-N-(4-methoxy-phenyl)-malonamic acid methyl ester 
• 57618-64-1 (2,3,4,5-Tetrachloro-cyclopenta-2,4-dienylidene-hydrazinocarbonyl)-acetic acid methyl ester 
• 154923-78-1 Malonic acid (1R,5S)-5-isopropenyl-2-methyl-cyclohex-2-enyl ester methyl ester 
• 142613-21-6 N-(4-Methoxy-phenyl)-N-phenethyl-malonamic acid methyl ester 
• 80546-70-9 3,5-dicloro-2-carbometossiacetilaminobenzensolfonamide 
• 142613-20-5 N-Butyl-N-(4-methoxy-phenyl)-malonamic acid methyl ester 
• 131925-11-6 N-(2-Methoxycarbonylacetamidophenyl)-N-methyl-1H-pyrrol-1-ylamine 
• 82031-42-3 N-(Methoxycarbonylacetyl)glycin-ethylester 
• 141987-84-0 (S)-3-(3,4-Dimethoxy-phenyl)-2-(2-methoxycarbonyl-acetylamino)-propionic acid methyl ester 
• 154227-82-4 1-(2-methoxycarbonylacetamidomethyl)phenyl-1H-pyrrole 
• 131072-36-1 Methyl <(R)-2-allyloxy-3-(4-methoxy-benzyloxy)-propyl> malonate 
• 130406-66-5 tricyclo<3.3.1.1^3,7>dec-2-yl *,R^*)>-3-(1H-indol-3-ylmethyl)-3-methyl-4,9,11-trioxo-7-phenyl-12-oxa-2,5,8-triazatridecanoate 
• 130406-55-2 tricyclo<3.3.1.1^3,7>dec-2-yl *,S^*)>-3-(1H-indol-3-ylmethyl)-3-methyl-4,9,11-trioxo-6-(phenylmethyl)-12-oxa-2,5,8-triazatridecanoate 

Relevant articles and documents

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