73246-45-4

Basic information

• Product Name: (S)-(-)-Methyl 2-chloropropionate
• Synonyms: 2-chloro-,methylester,(s)-propanoicaci;Methyl 2-chloropropanoate;(S)-(-)-2-CHLOROPROPIONIC ACID METHYL ESTER;(S)-2-CHLOROPROPIONIC ACID METHYL ESTER;S-2-CHLOROPROPANOIC ACID METHYL ESTER;(S)-(+)-METHYL 2-CHLOROPROPIONATE;Methyl L-chloropropionate;L(-)-2-Chloropropionate methyl ester
• CAS NO: 73246-45-4
• Molecular Formula: C₄H₇ClO₂
• Molecular Weight: 122.55
• EINECS: 412-470-8
• Product Categories: chiral;CHIRAL COMPOUNDS;Chiral Building Blocks;Esters (Chiral);Synthetic Organic Chemistry;Chiral Building Blocks;Esters;Organic Building Blocks
• Mol File: 73246-45-4.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 80-82 °C110 mm Hg(lit.)
• Flash Point: 101 °F
• Appearance: Colorless liquid
• Density: 1.143 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.417(lit.)
• Storage Temp.: -20°C
• BRN: 1720589
• CAS DataBase Reference: (S)-(-)-Methyl 2-chloropropionate(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(-)-Methyl 2-chloropropionate(73246-45-4)
• EPA Substance Registry System: (S)-(-)-Methyl 2-chloropropionate(73246-45-4)

Safety Data

• Hazard Codes: Xn
• Statements: 10-36-48/22
• Safety Statements: 23-26-36
• RIDADR: UN 2933 3/PG 3
• WGK Germany: 1
• F: 19
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 73246-45-4(Hazardous Substances Data)

Usage

Uses

(-)-Methyl α-Chloropropionate is used in the preparation of TIPTP which is a therapeutic agent for rheumatoid arthritis.

InChI:InChI=1/C4H7ClO2/c1-3(5)4(6)7-2/h3H,1-2H3/t3-/m0/s1

Synthetic route

(R)-Methyl lactate (17392-83-5) → methyl-(S)-2-chloropropionate (73246-45-4)

Conditions	Yield
With pyridine; thionyl chloride In N,N-dimethyl-formamide at 20 - 55℃; for 5h; Temperature; Reagent/catalyst; Solvent;	90%

(R)-Methyl lactate (17392-83-5) → methyl-(S)-2-chloropropionate (73246-45-4) + methyl (2R)-2-chloropropanoate (77287-29-7)

Conditions	Yield
With pyridine; thionyl chloride In N,N-dimethyl-formamide at 20 - 55℃; for 6h;	A 86% B n/a

(S)-Methyl lactate (27871-49-4) → methyl-(S)-2-chloropropionate (73246-45-4)

Conditions	Yield
With thionyl chloride at 100℃;	75%
With thionyl chloride In diethyl ether at 20℃; for 16h;	72%

methanol (67-56-1) + (S)-2-chloropropanoic acid (29617-66-1) → methyl-(S)-2-chloropropionate (73246-45-4)

Conditions	Yield
With thionyl chloride at 20℃; for 5h; Reflux;	66%
With boron trifluoride
With thionyl chloride optical yield given as %ee;	124 mg

diazomethane (186581-53-3, 908094-01-9) + (S)-2-chloropropanoic acid (29617-66-1) → methyl-(S)-2-chloropropionate (73246-45-4)

Conditions	Yield
With hexane

methanol (67-56-1) + L-Lactic acid (79-33-4) → methyl-(S)-2-chloropropionate (73246-45-4)

Conditions	Yield
With phosphorus pentachloride methyl ester of/the/ l-α-chloro-propionic acid;

methanol (67-56-1) + (S)-2-chloropropionyl chloride (70110-24-6) → methyl-(S)-2-chloropropionate (73246-45-4)

(R)-Methyl lactate (17392-83-5) → methyl-(S)-2-chloropropionate (73246-45-4) + methyl (2S)-2-bromopropanoate (20047-41-0, 57885-43-5, 5445-17-0, 62076-23-7)

Conditions	Yield
With pyridine; thionyl chloride; hydrogen bromide Yield given. Multistep reaction. Yields of byproduct given;

methyl (2R)-2-chloropropanoate (77287-29-7) → methyl-(S)-2-chloropropionate (73246-45-4)

Conditions	Yield
With N,N,N',N',N'',N''-hexamethylguanidinium chloride at 70℃; Product distribution; Further Variations:; Temperatures; Reagents;

methyl S-(-)-2-(chlorocarbonyloxy)propionate → methyl-(S)-2-chloropropionate (73246-45-4) + methyl (2R)-2-chloropropanoate (77287-29-7)

Conditions	Yield
With N,N,N',N',N'',N''-hexamethylguanidinium chloride at 70℃; Product distribution; Further Variations:; Temperatures; Reagents;

(R)-2-chloropropionic acid (7474-05-7) + diazomethyl-trimethyl-silane (18107-18-1) → methyl-(S)-2-chloropropionate (73246-45-4) + methyl (2R)-2-chloropropanoate (77287-29-7)

Conditions	Yield
In methanol; hexane; toluene for 0.0833333h; Title compound not separated from byproducts;

2-chloro-propionic acid methyl ester (17639-93-9) → methyl-(S)-2-chloropropionate (73246-45-4) + methyl (2R)-2-chloropropanoate (77287-29-7)

Conditions	Yield
With poly{N-[(1S,2S)-2-benzyloxycyclopentyl]maleimide} Resolution of racemate;

methyl 2-chloroacrylate (80-63-7) → methyl-(S)-2-chloropropionate (73246-45-4) + methyl (2R)-2-chloropropanoate (77287-29-7)

Conditions	Yield
With Saccharomyces cerevisiae Old Yellow Enzyme 3 ene-reductase; nicotinamine adenine dinucleotide at 30℃; for 24h; pH=7.5; aq. buffer; Enzymatic reaction; optical yield given as %ee; stereoselective reaction;

methyl-(S)-2-chloropropionate (73246-45-4) + hydroquinone (123-31-9) → (R)-(+)-2-(4-hydroxyphenoxy)propionic acid methyl ester (96562-58-2)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80 - 90℃; for 3h; Temperature;	95%

methyl-(S)-2-chloropropionate (73246-45-4) + potassium thioacetate (10387-40-3) → methyl (2R)‐2‐(acetylthio)propanoate (33302-03-3)

Conditions	Yield
In N,N-dimethyl-formamide at 20℃;	94.8%
In acetone

methyl-(S)-2-chloropropionate (73246-45-4) + 4-chloro-phenol (106-48-9) → (R)-2-(4-chlorophenoxy)propanoic acid (3307-39-9, 20421-33-4, 20421-35-6, 20421-34-5)

Conditions	Yield
Stage #1: 4-chloro-phenol With potassium hydroxide In water at 60℃; for 0.5h; Stage #2: methyl-(S)-2-chloropropionate In water at 60℃; for 4h; Reagent/catalyst;	92.2%

methyl-(S)-2-chloropropionate (73246-45-4) + cesium thioacetate (56827-86-2) → (S)-methyl 2-(acetylsulfanyl)propionate

Conditions	Yield
In N,N-dimethyl-formamide at 25℃;	89%

methyl-(S)-2-chloropropionate (73246-45-4) + thioacetic acid (507-09-5) → methyl (2R)‐2‐(acetylthio)propanoate (33302-03-3)

Conditions	Yield
Stage #1: tiolacetic acid With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: methyl-(S)-2-chloropropionate In N,N-dimethyl-formamide for 3h;	88%
Stage #1: tiolacetic acid With caesium carbonate In N,N-dimethyl-formamide for 0.5h; Stage #2: methyl-(S)-2-chloropropionate In N,N-dimethyl-formamide at 20℃; for 1h;	82%
Stage #1: tiolacetic acid With caesium carbonate In N,N-dimethyl-formamide for 0.5h; Stage #2: methyl-(S)-2-chloropropionate In N,N-dimethyl-formamide at 20℃; for 1h;	82%

methyl-(S)-2-chloropropionate (73246-45-4) + 2,2-Dimethyl-1,3-diaminopropane (7328-91-8) → dimethyl 2,2'-((2,2-dimethylpropane-1,3-diyl)bis(azanediyl))(2R,2'R)-dipropionate

Conditions	Yield
With potassium carbonate In acetonitrile for 24h; Reflux;	85.9%

methyl-(S)-2-chloropropionate (73246-45-4) + 9H-carbazole (86-74-8) → C16H15NO2

Conditions	Yield
Stage #1: 9H-carbazole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 25℃; for 1.5h; Inert atmosphere; Stage #2: methyl-(S)-2-chloropropionate In N,N-dimethyl-formamide; mineral oil at 25℃; for 12h; Inert atmosphere;	84%

4-bromo-1H-pyrazole (2075-45-8) + methyl-(S)-2-chloropropionate (73246-45-4) → 2-(4-bromo-pyrazol-1-yl)-propionic acid methyl ester (877399-68-3)

Conditions	Yield
Stage #1: 4-bromo-1H-pyrazole With sodium hydride In N,N-dimethyl-formamide for 0.166667h; Stage #2: methyl-(S)-2-chloropropionate In N,N-dimethyl-formamide for 4h;	77%

methyl-(S)-2-chloropropionate (73246-45-4) + 5-(3-(3-ethyl-4-(2-(piperidin-4-yl)ethoxy)phenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-3-(trifluoromethyl)picolinonitrile hydrochloride → (R)-methyl 2-(4-(2-(4-(3-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperidin-1-yl)propanoate

Conditions	Yield
With triethylamine In tetrahydrofuran at 85℃; for 48h;	76%

methyl-(S)-2-chloropropionate (73246-45-4) + [(Ir(μ-pyrazolate)(CNBu(t))2)2] (185223-00-1) → (+/-)-[(CNBu-t)2(Cl)Ir(μ-pyrazolato)2Ir(η1-CH(Me)CO2Me)(CNBu-t)2] (203636-13-9, 315178-95-1)

Conditions	Yield
In benzene CH3CO2CH(CH3)Cl was added to a soln. of complex in benzene, 30 min in the dark (Ar); the soln. was layered with hexane, allowed to stand 2 d in the darkness, crystals were sepd. by decantation, washed with cold hexane and vac.-dried; elem. anal.;	65%

methyl-(S)-2-chloropropionate (73246-45-4) + hexafluoroacetone oxime (1645-76-7) → (R)-2-(2,2,2-Trifluoro-1-trifluoromethyl-ethylideneaminooxy)-propionic acid methyl ester (213010-46-9)

Conditions	Yield
With potassium carbonate In acetonitrile 1) 0-5 deg C, 10 h; 2) 20 deg C, 10 h;	64%

methyl-(S)-2-chloropropionate (73246-45-4) + methyl 2,4,6-tri-O-benzyl-β-D-galactopyranoside (55697-53-5) → (R)-2-((2R,3S,4S,5R,6R)-3,5-Bis-benzyloxy-2-benzyloxymethyl-6-methoxy-tetrahydro-pyran-4-yloxy)-propionic acid methyl ester (177421-03-3) + (S)-2-((2R,3S,4S,5R,6R)-3,5-Bis-benzyloxy-2-benzyloxymethyl-6-methoxy-tetrahydro-pyran-4-yloxy)-propionic acid methyl ester (177421-02-2)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide 1.) 60 deg C, 1 h, 2.) 60 deg C, 24 h;	A 8.4% B 57.2%

carbon disulfide (75-15-0) + methyl-(S)-2-chloropropionate (73246-45-4) + (2R)-methoxymethylpyrrolidine (63126-47-6, 76946-27-5, 84025-81-0, 135523-48-7) → 2(R)-((R)-2-Methoxymethylpyrrolidin-1-ylthiocarbonylthio)-propansaeuremethylester

Conditions	Yield
With sodium acetate In methanol	56.8%

methyl-(S)-2-chloropropionate (73246-45-4) + 4-(3-(3-chloro-4-(2-(piperazin-1-yl)ethoxy)phenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile hydrochloride → (R)-methyl 2-(4-(2-(2-chloro-4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)phenoxy)ethyl)piperazin-1-yl)propanoate

Conditions	Yield
With triethylamine In tetrahydrofuran at 80℃; for 6h;	48.4%

methyl-(S)-2-chloropropionate (73246-45-4) + 4-(3-(3-ethyl-4-(2-(piperidin-4-yl)ethoxy)phenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile + trifluoroacetic acid (76-05-1) → (R)-methyl 2-(4-(2-(4-(3-(4-cyano-3-(trifluoromethyl)phenyl)-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl)-2-ethylphenoxy)ethyl)piperidin-1-yl)propanoate trifluoroacetate

Conditions	Yield
Stage #1: methyl-(S)-2-chloropropionate; 4-(3-(3-ethyl-4-(2-(piperidin-4-yl)ethoxy)phenyl)-4,4-dimethyl-5-oxo-2-thioxoimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile With triethylamine In tetrahydrofuran at 85℃; for 48h; Stage #2: trifluoroacetic acid In acetonitrile	47.5%

carbon disulfide (75-15-0) + methyl-(S)-2-chloropropionate (73246-45-4) + (2S)-2-(methoxymethyl)-1-pyrrolidine (63126-47-6) → 2(R)-((S)-2-Methoxymethylpyrrolidin-1-ylthiocarbonylthio)-propansaeuremethylester

Conditions	Yield
With sodium acetate In methanol	47.3%

methyl-(S)-2-chloropropionate (73246-45-4) + 3-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenol → methyl (R)-2-(3-(4,5,6,7-tetrahydro-2H-indazol-2-yl)phenoxy)propanoate

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 6h; Inert atmosphere;	39%

methyl-(S)-2-chloropropionate (73246-45-4) + ethanolamine (141-43-5) → 2-methyl-morpholin-3-one (13882-80-9)

Conditions	Yield
With sodium In 1,4-dioxane for 3h; Reflux;	14.2%

methyl-(S)-2-chloropropionate (73246-45-4) + (R)-methyl p-tolyl sulfoxide (1519-39-7) → (+)-SC,RS-3-chloro-1-(4-methylphenyl)sulphinyl-2-butanone (104891-12-5)

methyl-(S)-2-chloropropionate (73246-45-4) + methyl (2S)-2-amino-3-phenylpropanoate hydrochloride (7524-50-7) → (2S,2'R)-dimethyl 3-phenyl-2,2'-iminodipropionate

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 80 - 100℃; for 48h;

methyl-(S)-2-chloropropionate (73246-45-4) + aluminum isopropoxide (555-31-7) → iso-propyl-2-chloropropanoate (40058-87-5)

Conditions	Yield
at 25℃; Product distribution; also with titanium isopropoxide;

methyl-(S)-2-chloropropionate (73246-45-4) → methanol (67-56-1) + (S)-2-chloropropanoic acid (29617-66-1)

Conditions	Yield
subtilisin In water at 30℃; Kinetics;
With 2-(di(2-hydroxyethyl)amino)ethanesulfonic acid; esterase from Pseudomonas fluorescens In water at 25℃; pH=7.20; Enzyme kinetics;
With 2-(di(2-hydroxyethyl)amino)ethanesulfonic acid; lipase from Ophiostoma piliferum In water at 25℃; pH=7.20; Enzyme kinetics;
With 2-(di(2-hydroxyethyl)amino)ethanesulfonic acid; lipase from Bacillus thermocatenulanatus In water at 40℃; pH=7.20; Enzyme kinetics;

Upstream product

• 186581-53-3 diazomethane 
• 29617-66-1 (S)-2-chloropropanoic acid 
• 67-56-1 methanol 
• 79-33-4 L-Lactic acid 
• 70110-24-6 (S)-2-chloropropionyl chloride 
• 77287-29-7 methyl (2R)-2-chloropropanoate 
• 17639-93-9 2-chloro-propionic acid methyl ester 
• 121769-68-4 [9,9']Biphenanthrenyl-10,10'-diol; compound with 2-chloro-propionic acid methyl ester 
• 121769-68-4 [9,9']Biphenanthrenyl-10,10'-diol; compound with 2-chloro-propionic acid methyl ester 
• 17392-83-5 (R)-Methyl lactate 
• 80-63-7 methyl 2-chloroacrylate 
• 7474-05-7 (R)-2-chloropropionic acid 
• 18107-18-1 diazomethyl-trimethyl-silane 
• 27871-49-4 (S)-Methyl lactate 

Downstream Products

• 104891-12-5 (+)-S_C,R_S-3-chloro-1-(4-methylphenyl)sulphinyl-2-butanone 
• 40058-87-5 iso-propyl-2-chloropropanoate 
• 67-56-1 methanol 
• 29617-66-1 (S)-2-chloropropanoic acid 
• 17639-76-8 methyl 2-methoxypropionate 
• 93940-07-9 N,N-Diethyl-2-methoxy-propionamide 
• 177421-03-3 (R)-2-((2R,3S,4S,5R,6R)-3,5-Bis-benzyloxy-2-benzyloxymethyl-6-methoxy-tetrahydro-pyran-4-yloxy)-propionic acid methyl ester 
• 177421-02-2 (S)-2-((2R,3S,4S,5R,6R)-3,5-Bis-benzyloxy-2-benzyloxymethyl-6-methoxy-tetrahydro-pyran-4-yloxy)-propionic acid methyl ester 
• 185298-43-5 (R)-2-(1-Benzyl-2-ethyl-1H-indol-4-yloxy)-propionic acid methyl ester 
• 95977-29-0 (R)-2-[4-(3-chloro-5-trifluoromethylpyridin-2-yloxy)phenoxy]propanoic acid 
• 932709-56-3 (R)-2-[3-(2,4-dichlorobenzyl)-8-fluoro-4-methyl-2-oxo-1,2-dihydroquinolin-5-yloxy]propionic acid methyl ester 
• 13882-80-9 2-methyl-morpholin-3-one 
• 3307-39-9 (R)-2-(4-chlorophenoxy)propanoic acid 

Relevant articles and documents

Optical methyl 2-chloropropionate synthesis by decomposition of methyl 2-(chlorocarbonyloxy)propionate with hexaalkylguanidinium chloride hydrochloride

The decomposition of methyl S-(-)-2-(chlorocarbonyloxy)propionate in the presence of hexaalkylguanidinium chloride hydrochloride was confirmed to correspond to a nucleophilic substitution of the second order. However, racemization occured by the contact between the catalyst and methyl R-(+)-2-chloropropionate (I). This phenomenon is caused by the exchange between the chloride ion from catalyst and the chlorine atom of (I) according to a SN2 mechanism as well.

A synthetic S-2-chloropropionic acid methyl ester method

The invention discloses a method for synthesizing S-2-methyl chloropropionate. The method comprises the following steps of: (1) preparing a Vilmerier reagent: adding a chlorinating agent into a reaction kettle, adding short chain aliphatic series dropwise to replace amide to serve as a solvent, and reacting under the stirring condition to obtain a Vilmerier reagent solution; (2) synthesizing S-2-methyl chloropropionate: adding a small amount of solvent into the Vilmerier reagent solution obtained in the step 1 to obtain a mixed solution, adding R-methyl lactate into the mixed solution dropwise, and stirring to perform chlorination to obtain a product solution, namely the S-2-methyl chloropropionate solution; and (3) washing the S-2-methyl chloropropionate solution obtained in the step 2, desolventizing and distilling to obtain the product S-2-methyl chloropropionate. The synthesis method is mild in reaction condition, easy to operate, low in environmental pollution and suitable for large-scale industrialized production.

Optically active maleimide derivatives and polymaleimides for use as chiral adsorbent in chromatography

An optically active maleimide dericative represented by the following formula (1): as well as the polymer synthesized therefrom. The polymers are useful as chival adsorbents in chomatography.