3153-37-5

Basic information

• Product Name: Methyl 4-chlorobutyrate
• Synonyms: Butanoic acid, 4-chloro-, methyl ester;Butyric acid, 4-chloro-, methyl ester;ClCH2(CH2)2C(O)OCH3;gamma-Chlorobutyric acid methyl ester;Methyl 4-chlorobutanoate;Methyl gamma-chlorobutyrate;Methyl omega-chlorobutyrate;methyl4-chlorobutanoate
• CAS NO: 3153-37-5
• Molecular Formula: C₅H₉ClO₂
• Molecular Weight: 136.58
• EINECS: 221-592-9
• Product Categories: Aromatic Esters;C2 to C5;Carbonyl Compounds;Esters
• Mol File: 3153-37-5.mol
• Article Data: 11

Chemical Properties

• Boiling Point: 175-176 °C(lit.)
• Flash Point: 139 °F
• Appearance: Clear colorless/Liquid
• Density: 1.12 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.14mmHg at 25°C
• Refractive Index: n20/D 1.433(lit.)
• Storage Temp.: 2-8°C
• Water Solubility: Slightly soluble in water.
• BRN: 1745117
• CAS DataBase Reference: Methyl 4-chlorobutyrate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl 4-chlorobutyrate(3153-37-5)
• EPA Substance Registry System: Methyl 4-chlorobutyrate(3153-37-5)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26
• RIDADR: UN 3272 3/PG 3
• WGK Germany: 3
• TSCA: Yes
• HazardClass: 3
• PackingGroup: III
• Hazardous Substances Data: 3153-37-5(Hazardous Substances Data)

Usage

Chemical Properties

clear colourless liquid

Uses

Methyl 4-chlorobutyrate is used as a pharmaceutical synthesis, industrial dye intermediates.

InChI:InChI=1/C5H9ClO2/c1-8-5(7)3-2-4-6/h2-4H2,1H3

Synthetic route

4-butanolide (96-48-0) + methanol (67-56-1) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
Stage #1: 4-butanolide With dichlorotriphenoxyphosphorane In dichloromethane at -5 - 0℃; Stage #2: methanol In dichloromethane at 45 - 50℃; Temperature;	93.1%

methanol (67-56-1) + 4-Chlorobutanoyl chloride (4635-59-0) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With pyridine at 25℃; for 18h;	77%

5-chloro-2-pentanone (5891-21-4) + acetic anhydride (108-24-7) → methyl 4-chlorobutyrate (3153-37-5) + methyl 3-chloropropionate (6001-87-2)

Conditions	Yield
With oxygen; manganese(III) triacetate dihydrate at 90℃; under 3750.38 Torr; for 10h; Autoclave;	A 76% B 14%

methanol (67-56-1) + 4-Chlorobutyronitrile (628-20-6) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With hydrogenchloride

methanol (67-56-1) + γ-chlorobutyric acid (627-00-9) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With sulfuric acid; benzene
With sulfuric acid

methanol (67-56-1) + 4-hydroxy-1-butanitrile (628-22-8) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With hydrogenchloride

methanol (67-56-1) + 4-(4-nitrophenoxy)butanoic acid (28341-54-0) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With hydrogenchloride; zinc(II) chloride anfangs unter Eiskuehlung, zuletzt bei Siedetemperatur;

butanoic acid methyl ester (623-42-7) → 2-chloropropyl methyl ester (817-76-5) + methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With N-chloropiperidine; 2,2'-azobis(isobutyronitrile) In trifluoroacetic acid at 30℃; Product distribution; Rate constant; Irradiation; relative rate constants, position selectivity, substrate selectivity;
With chlorine Irradiation.mit UV-Licht;

butanoic acid methyl ester (623-42-7) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With chlorine Irradiation.Dampfphase; UV-Licht;

4-methoxy-butyryl chloride (61882-39-1) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
3-stdg. Erwarmen auf dem Dampfbad;

4-methoxybutyric acid (29006-02-8) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With thionyl chloride

γ-Diazobuttersaeure-methylester (591235-25-5) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With hydrogenchloride In diethyl ether

butanoic acid methyl ester (623-42-7) → methyl 2-chlorobutanoate (26464-32-4, 149948-70-9, 149948-80-1) + 2-chloropropyl methyl ester (817-76-5) + chloromethyl n-butyrate (33657-49-7) + methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
With chlorine Product distribution; Heating; Irradiation; influence of temperature, chlorinating agent, UV, addition of benzoyl peroxide;	A 8 % Chromat. B 52 % Chromat. C 2 % Chromat. D 38 % Chromat.

hydrogenchloride (7647-01-0) + 4-Chlorobutyronitrile (628-20-6) → methyl 4-chlorobutyrate (3153-37-5)

thionyl chloride (7719-09-7) + 4-methoxybutyric acid (29006-02-8) → methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
auf dem Dampfbad;

butanoic acid methyl ester (623-42-7) + chlorine (7782-50-5) → 2-chloropropyl methyl ester (817-76-5) + methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
Behandeln des Dampfes im UV-Licht.Irradiation;

sulfuryl dichloride (7791-25-5) + butanoic acid methyl ester (623-42-7) + dibenzoyl peroxide (94-36-0) → methyl 2-chlorobutanoate (26464-32-4, 149948-70-9, 149948-80-1) + 2-chloropropyl methyl ester (817-76-5) + methyl 4-chlorobutyrate (3153-37-5)

Conditions	Yield
im Dunkeln;

methyl 4-chlorobutyrate (3153-37-5) → methyl-γ-azidobutyrate (87517-47-3)

Conditions	Yield
With sodium azide In dimethyl sulfoxide at 45℃; for 24h;	99%
With sodium azide In dimethyl sulfoxide at 45 - 50℃; for 24h;	95%
With sodium azide In dimethyl sulfoxide at 60℃; for 18h;	85%

1-methyl-1H-imidazole (616-47-7) + methyl 4-chlorobutyrate (3153-37-5) → 1-(3-methoxycarbonyl-propyl)-3-methyl-3H-imidazol-1-ium; chloride

Conditions	Yield
at 60℃; for 24h;	97%

methyl magnesium iodide (917-64-6) + methyl 4-chlorobutyrate (3153-37-5) → 5-chloro-2-methylpentan-2-ol (7712-59-6)

Conditions	Yield
In tetrahydrofuran; diethyl ether at 20 - 45℃; Grignard reaction; Inert atmosphere;	95%
In diethyl ether	78%

methyl 4-chlorobutyrate (3153-37-5) + 1-(Trimethylsilyl)imidazole (18156-74-6) → 1,3-bis-(3-methoxycarbonyl-propyl)-3H-imidazol-1-ium; chloride

Conditions	Yield
at 60℃; for 24h;	95%

1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one (52099-72-6) + methyl 4-chlorobutyrate (3153-37-5) → 4-(1,2-dihydro-2-oxobenzo[d]imidazole-3-yl)butanoic acid (3273-68-5)

Conditions	Yield
Stage #1: 1,3-dihydro-1-(1-methylethenyl)-2H-benzimidazol-2-one; methyl 4-chlorobutyrate With tetrabutylammomium bromide; potassium carbonate; potassium iodide In dimethyl sulfoxide at 110 - 115℃; Stage #2: With water; sodium hydroxide at 95 - 100℃; for 6h; Stage #3: With hydrogenchloride In water at 80 - 85℃;	95%

methyl 4-chlorobutyrate (3153-37-5) + 1-adamantanemethanol (770-71-8) → 4-Chloro-butyric acid adamantan-1-ylmethyl ester

Conditions	Yield
With n-butylstannoic acid In toluene for 22h; Heating;	94%

methyl 4-chlorobutyrate (3153-37-5) + (S)-2-amino-butanamide hydrochloride (53726-14-0) → levetiracetam (102767-28-2)

Conditions	Yield
With potassium carbonate; potassium iodide In dimethyl sulfoxide at 100℃; for 24h; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	80%

6-benzyloxy-2-(4-hydroxyphenyl)-3-[3-methoxy-4-[(1-pyrrolidinyl)methyl]benzyl]benzo[b]thiophene (193966-79-9) + methyl 4-chlorobutyrate (3153-37-5) → 6-Benzyloxy-3-[3-methoxy-4-(1-pyrrolidinylmethyl)benzyl]-2-[4-[4-methoxy-4-oxobutoxy]phenyl]benzo[b]thiophene

Conditions	Yield
With caesium carbonate In water; ethyl acetate; N,N-dimethyl-formamide	78%
With caesium carbonate In N,N-dimethyl-formamide

methyl 4-chlorobutyrate (3153-37-5) + 1H-indazole-3-carboxamide (90004-04-9) → methyl 4-(3-carbamoyl-1H-indazol-1-yl) butyrate (1376660-66-0)

Conditions	Yield
With potassium carbonate In acetonitrile Reflux;	78%

methyl 4-chlorobutyrate (3153-37-5) + sodium salt of 3,5,6-trichloropyridine-2-ol → C10H10Cl3NO3

Conditions	Yield
With tetrabutylammomium bromide; sodium carbonate In N,N-dimethyl-formamide at 70℃; for 6h;	78%

methyl 4-chlorobutyrate (3153-37-5) → methyl 4-iodobutanoate (14273-85-9)

Conditions	Yield
With sodium iodide In acetone for 42h; Heating;	77.5%
With sodium iodide In acetone Heating; Yield given;
With sodium iodide In acetone

methyl 4-chlorobutyrate (3153-37-5) + 1-diethoxyphosphoryl-2-(β-hydroxyethyl)aminoethane (942596-86-3) → methyl 3-((2-(diethoxyphosphoryl)ethyl)(2-hydroxyethyl)amino)butanoate (1383381-59-6)

Conditions	Yield
With potassium carbonate In acetonitrile at -10 - 80℃; for 70h;	77%
With potassium carbonate In acetonitrile at -10 - 80℃; for 71h;	77%

methyl 4-chlorobutyrate (3153-37-5) + (trimethylsilyl)methylmagnesium chloride (13170-43-9) → 5-chloro-2-(trimethylsilylmethyl)-pent-1-ene (121896-55-7)

Conditions	Yield
With cerium(III) chloride	76%

methyl 4-chlorobutyrate (3153-37-5) + Benzimidazol-2-thiol (134469-07-1) → methyl 4-((1H-benzo[d]imidazol-2-yl)thio)butanoate

Conditions	Yield
With potassium hydroxide In N,N-dimethyl-formamide at 20℃;	76%

styrene (292638-84-7) + methyl 4-chlorobutyrate (3153-37-5) + 2-iodobiphenyl (2113-51-1) → methyl (E)-4-(2'-styryl-[1,1'-biphenyl]-2-yl)butanoate

Conditions	Yield
With potassium acetate; palladium diacetate; potassium carbonate; isopropyl alcohol In N,N-dimethyl-formamide at 70℃; for 12h; Schlenk technique; Inert atmosphere;	73%

methyl 4-chlorobutyrate (3153-37-5) + benzaldehyde (100-52-7) → 4-Chloro-2-(hydroxy-phenyl-methyl)-butyric acid methyl ester (214424-65-4)

Conditions	Yield
Stage #1: methyl 4-chlorobutyrate; benzaldehyde With potassium tert-butylate In tetrahydrofuran at -75℃; Aldol type addition; Inert atmosphere; Stage #2: With water; ammonium chloride In tetrahydrofuran Inert atmosphere;	71%

methyl 4-chlorobutyrate (3153-37-5) + 2-tert-butylbromobenzene (7073-99-6) → methyl 4-(8,8-dimethylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)butanoate

Conditions	Yield
With palladium diacetate; potassium carbonate; tris-(o-tolyl)phosphine In N,N-dimethyl-formamide at 70℃; for 24h; Schlenk technique; Inert atmosphere; Sealed tube;	71%

methyl 4-chlorobutyrate (3153-37-5) + ethyl 3-methyl-5-oxo-2,5-dihydroisoxazole-4-carboxylate sodium salt (133827-52-8) → 2-(3-Methoxycarbonyl-propyl)-3-methyl-5-oxo-2,5-dihydro-isoxazole-4-carboxylic acid ethyl ester (113768-53-9)

Conditions	Yield
With sodium iodide In N,N-dimethyl-formamide at 110 - 120℃; for 3h;	70%

4-(benzyloxy)pyridin-2(1H)-one (53937-02-3) + methyl 4-chlorobutyrate (3153-37-5) → 4-(4-Benzyloxy-2-oxo-2H-pyridin-1-yl)-butyric acid methyl ester (219954-12-8)

Conditions	Yield
With potassium carbonate In acetonitrile for 48h; Heating;	68%

Upstream product

• 67-56-1 methanol 
• 628-20-6 4-Chlorobutyronitrile 
• 627-00-9 γ-chlorobutyric acid 
• 628-22-8 4-hydroxy-1-butanitrile 
• 28341-54-0 4-(4-nitrophenoxy)butanoic acid 
• 623-42-7 butanoic acid methyl ester 
• 61882-39-1 4-methoxy-butyryl chloride 
• 29006-02-8 4-methoxybutyric acid 
• 591235-25-5 ω-Diazo-buttersaeuremethylester 
• 4635-59-0 4-Chlorobutanoyl chloride 
• 7647-01-0 hydrogenchloride 
• 7719-09-7 thionyl chloride 
• 7782-50-5 chlorine 
• 7791-25-5 sulfuryl dichloride 

Downstream Products

• 2327-68-6 <3-Methoxycarbonyl-propyl>-phosphonsaeure-diaethylester 
• 63645-18-1 4-hydroxy-4,4-diphenylbutyl chloride 
• 140160-86-7 methyl 4-<3-(p-t-butylphenyl)-2-methylpropylthio>butanoate 
• 6139-84-0 4-chlorobutyraldehyde 
• 14273-85-9 methyl 4-iodobutanoate 
• 2046-17-5 methyl 3-(benzyl)propanoate 
• 10385-30-5 4-(benzyloxy)butanoic acid 
• 49802-81-5 4-[2-(4-Chloro-phenoxy)-2-methyl-propionyloxy]-butyric acid methyl ester 
• 219954-12-8 4-(4-Benzyloxy-2-oxo-2H-pyridin-1-yl)-butyric acid methyl ester 
• 28341-54-0 4-(4-nitrophenoxy)butanoic acid 
• 216167-95-2 butanoic acid, 4-[4-[[1-[[3,5-bis(1,1-dimethylethyl)4-hydroxyphenyl]thio]-1-methylethyl]-thio]-2,6-bis(1,1-dimethylethyl)phenoxy] 
• 1085783-84-1 methyl 3-(7-oxo-2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}-6,7-dihydro[1,3]thiazolo[4,5-d]pyrimidin-5-yl)propanoate 
• 6249-56-5 γ-butyrobetaine hydrochloride 
• 1290572-55-2 dimethyl 4,4'-((2,5-bis((triisopropylsilyl)ethynyl)-1,4-phenylene)bisoxy)dibutanoate 

Relevant articles and documents

Preparation method of methyl 4-chlorobutyrate

The invention discloses a preparation method of methyl 4-chlorobutyrate and belongs to the field of synthesis of compounds. The preparation method using gamma-butyrolactone as a raw material comprisesthe steps of adding the gamma-butyrolactone into dichloromethane mixed liquid of triphenyl dichlorophosphate to carry out chlorination; adding methanol to carry out esterification to obtain methyl 4-chlorobutyrate. The preparation method is simple to perform, good in product quality, high in yield and green, produces nearly no three wastes and is suitable for industrial production.

Stereocontrolled construction of 1, 7-dimethyl A.B.C.[6.6.6] tricycles. Part I. transannular Diels-Alder reactions of 14-membered macrocycles containing frans-dienophiles

Transannular Diels-Alder reactions of 14-membered macrocyclic trienes possessing a methyl substituent on both the diene and dienophile moiety have been investigated. Macrocyclic structures la, lb, and lc having cis-trans-trans (CTT), trans-cis-trans (TCT), and trans-trans-trans (TTT) geometries could be stereoselectively constructed by coupling appropriately functionalized dienes 5 and dienophile 4 following an intramolecular displacement of an allylic halide by the anion of an appropriately located dimethyl malonate unit. The transannular Diels-Alder reaction performed on la led to a mixture of four major tricyclic products, including 34 possessing the unexpected trans-anti-cis (TAC) stereochemistry. When heated at 300°C, macrocycle lb underwent an unique conversion via an ene-retroene, Diels-Alder process, producing the unexpected tricycle 41 (racemic form) containing five contiguous chiral centers. A rationale for the above experimental facts is presented. In contrast to the previous results, the transannular Diels-Alder reaction of macrocycle lc was straightforward, producing a 95% isolated yield of trans-anti-cis (TAC) tricycle 34. This investigation demonstrates a general methodology for the stereocontrolled synthesis of 1, 2-dimethyl A.B.C[6.6.6] tricyclic compounds, which are potential precursors to polycyclic natural products such as steroids and terpenes.

MECHANISMS OF FREE-RADICAL REACTIONS. XXIV. QUANTITATIVE DESCRIPTION OF THE POLAR EFFECTS OF SUBSTITUENTS ON THE KINETICS OF THE FREE-RADICAL CHLORINATION OF ALIPHATIC COMPOUNDS BY N-CHLOROPIPERIDINE

The free-radical chlorination of 1-substituted alkanes with electron-withdrawing substituents by N-chloropiperidine in trifluoroacetic acid was studied by the method of competing reactions, and the relative rate constants were obtained for all positions of the substrates.The data on the position selectivity can be described satisfactorily by means of an electrostatic model of the polar effect of the substituent, calculated according to the Kirkwood-Westheimer equation.The obtained characteristics of the electrostatic effect can be successfully applied to calculation of the substrate selectivity and the intermolecular relative rate constants for all the positions, beginning with the third.The Taft equation is unsuitable for description of the effect of substituents on the reaction rate.