623-43-8

Basic information

• Product Name: trans-Methyl crotonate
• Synonyms: METHYICROTONATE;Methyl (E)-but-2-enoate;Methyl E-propene-1-carboxylate;trans-Methyl crotonate (E)-2-Butenoic acid methyl ester;(2E)-2-Butenoic acid methyl ester;(E)-2-Butenoic acid methyl;Crotonic acid methyl;trans-Methyl crotonate,98%
• CAS NO: 623-43-8
• Molecular Formula: C₅H₈O₂
• Molecular Weight: 100.12
• EINECS: 210-793-7
• Product Categories: C2 to C5;Carbonyl Compounds;Esters;Building Blocks;C2 to C5;Carbonyl Compounds;Chemical Synthesis;Organic Building Blocks;Fine Chemical
• Mol File: 623-43-8.mol
• Article Data: 81

Chemical Properties

• Melting Point: -42°C
• Boiling Point: 118-120 °C(lit.)
• Flash Point: 40 °F
• Appearance: Clear colorless/Liquid
• Density: 0.944 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.152mmHg at 25°C
• Refractive Index: n20/D 1.423(lit.)
• Storage Temp.: Flammables area
• Water Solubility: IMMISCIBLE
• Merck: 14,2597
• BRN: 1720292
• CAS DataBase Reference: trans-Methyl crotonate(CAS DataBase Reference)
• NIST Chemistry Reference: trans-Methyl crotonate(623-43-8)
• EPA Substance Registry System: trans-Methyl crotonate(623-43-8)

Safety Data

• Hazard Codes: F,Xi
• Statements: 11-36/37/38
• Safety Statements: 16-26-36-9-33
• RIDADR: UN 3272 3/PG 2
• WGK Germany: 2
• RTECS: GQ5710000
• TSCA: Yes
• HazardClass: 3
• PackingGroup: II
• Hazardous Substances Data: 623-43-8(Hazardous Substances Data)

Usage

Synthesis

Trans-Methyl crotonate is obtained by esterification of crotonic acid and methanol. The reaction solution prepared by 800g of crotonic acid, 1L of methanol, 130g of sulfuric acid and 300ml of carbon tetrachloride was heated on a water bath, and carbon tetrachloride was recovered after dehydration and esterification to obtain a crude product of methyl crotonate. Then, the unreacted crotonic acid in the crude product is washed with water, washed with 5% sodium carbonate, and purified by vacuum distillation to obtain the finished product.

Chemical Properties

CLEAR COLOURLESS LIQUID

Uses

Methyl crotonate was used to investigate chemo selectivity in the reaction between methyl crotonate and benzyl amine catalyzed by lipase B from Candida Antarctica using solvent engineering. It was used as starting reagent during the total synthesis of phytotoxins solanapyrones D(1) and E(2).

Synthesis Reference(s)

Tetrahedron Letters, 14, p. 2967, 1973 DOI: 10.1016/S0040-4039(01)96294-X

General Description

Methyl crotonate undergoes vinylogous aldol reaction with enolizable aldehydes in the presence of aluminum tris(2,6-di-2-naphthylphenoxide).

InChI:InChI=1/C5H8O2/c1-3-4(2)5(6)7/h3H,1-2H3,(H,6,7)/p-1/b4-3+

Synthetic route

methanol (67-56-1) + (E)-but-2-enoic acid (107-93-7) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With sulfuric acid for 0.25h; Esterification; Irradiation;	94%
With sulfuric acid for 12h; Heating;	82%
With thionyl chloride

methanol (67-56-1) + 2-(diethylamino)ethyl crotonate (84115-05-9) → crotonic acid methyl ester (623-43-8) + 2-(Diethylamino)ethanol (100-37-8)

Conditions	Yield
With toluene-4-sulfonic acid for 4h; Heating;	A 90% B 82%

2-(diethylamino)ethyl crotonate (84115-05-9) → crotonic acid methyl ester (623-43-8) + 2-(Diethylamino)ethanol (100-37-8)

Conditions	Yield
With methanol; toluene-4-sulfonic acid for 4h; Heating;	A 90% B 82%

2-ethylthio methyl ester (36056-36-7) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With tetrabutylammomium bromide; ammonium chloride In ethanol electrolysis;	90%

methanol (67-56-1) + crotonaldehyde (123-73-9) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With perchloric acid; sodium percarbonate; vanadia for 1h; Heating;	90%
With tert.-butylhydroperoxide In decane at 25℃; for 8h; Inert atmosphere;	72%

methyl 2,3-dibromobutyrate (5469-24-9) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With sodium tetrahydroborate; nickel dichloride In tetrahydrofuran at 20℃; for 0.583333h;	90%

wt.-% NaOH + wt.-% sodium methylate + water (7732-18-5) + 3-chloroprop-1-ene (107-05-1) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
Ni(CO)4 In methanol; aqueous KCl	90%

sodium methylate (124-41-4) + 2-Chloro-2-(1-chloroethyl)oxirane (51107-31-4) → Methyl β-methoxybutyrate (3136-17-2, 117745-43-4, 117745-47-8) + crotonic acid methyl ester (623-43-8) + ethylglyoxal dimethylacetal (6342-57-0)

Conditions	Yield
In methanol	A 11% B 3% C 86%
In methanol	A 11 % Chromat. B 3 % Chromat. C 86 % Chromat.
In methanol Product distribution; -50 deg C, then 3h, roomtemp.;	A 11 % Chromat. B 3 % Chromat. C 86 % Chromat.

erythro 2,3-dibromo-butenoate (5469-24-9, 22426-04-6, 26708-42-9, 99570-24-8, 99570-28-2) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With indium(III) chloride; sodium tetrahydroborate In acetonitrile at -10℃; for 3h;	78%

methyl-4-bromo-2-butenoate (1117-71-1, 56699-18-4, 6000-00-6) → crotonic acid methyl ester (623-43-8) + methyl but-3-enoate (3724-55-8) + 5-Vinyl-trans-hexen-2-disaeuredimethylester (26474-34-0)

Conditions	Yield
With zinc In dimethyl sulfoxide for 4h; Yields of byproduct given;	A n/a B n/a C 75%

dimethylsulfite (616-42-2) + (E)-but-2-enoic acid (107-93-7) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
sulfuric acid In methanol for 2h; Heating;	73%

methanol (67-56-1) + 2-piperidinoethyl trans-crotonate (84115-06-0) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With toluene-4-sulfonic acid for 3.5h; Heating;	72%

(E)-but-2-enoic acid (107-93-7) + Fe(ClO4)3(CH3OH)6/SiO2 → crotonic acid methyl ester (623-43-8)

Conditions	Yield
for 2h; Solid phase reaction; esterification;	66%

1-phenylmethylenecyclopropane (7555-67-1) + pentacrbonyl[(1-methoxy-1-(2-methylethenyl)carbene]chromium(0) → 2-Methoxy-3-[1-phenyl-meth-(E)-ylidene]-2-((E)-propenyl)-cyclopentanone + crotonic acid methyl ester (623-43-8)

Conditions	Yield
With bis(1,5-cyclooctadiene)nickel (0) In N,N-dimethyl-formamide at 0℃; for 1h;	A 55% B n/a

sodium methylate (124-41-4) + 1,3-dichlorobutan-2-one (16714-77-5) → Methyl β-methoxybutyrate (3136-17-2, 117745-43-4, 117745-47-8) + (Z)-methyl but-2-enoate (4358-59-2) + crotonic acid methyl ester (623-43-8) + ethylglyoxal dimethylacetal (6342-57-0)

Conditions	Yield
In methanol -50 deg C, then 3h, roomtemp.; Further byproducts given;	A 13% B 36% C 16% D 16%

sodium methylate (124-41-4) + 1,3-dichlorobutan-2-one (16714-77-5) → Methyl β-methoxybutyrate (3136-17-2, 117745-43-4, 117745-47-8) + (Z)-methyl but-2-enoate (4358-59-2) + crotonic acid methyl ester (623-43-8) + ethylglyoxal dimethylacetal (6342-57-0) + methacrylic acid methyl ester (80-62-6)

Conditions	Yield
In methanol Product distribution; -50 deg C, then 3h, roomtemp.;	A 13% B 36% C 16% D 16% E 13%

sodium methylate (124-41-4) + 1,3-dichlorobutan-2-one (16714-77-5) → (Z)-methyl but-2-enoate (4358-59-2) + crotonic acid methyl ester (623-43-8) + ethylglyoxal dimethylacetal (6342-57-0) + methacrylic acid methyl ester (80-62-6)

Conditions	Yield
In methanol -50 deg C, then 3h, roomtemp.; Further byproducts given;	A 36% B 16% C 16% D 13%

allyl methyl carbonate (35466-83-2) + carbon monoxide (201230-82-2) → crotonic acid methyl ester (623-43-8) + methyl but-3-enoate (3724-55-8)

Conditions	Yield
With 1,10-Phenanthroline; dodecacarbonyl-triangulo-triruthenium at 120℃; under 30400 Torr; for 10h; Yields of byproduct given;	A 18% B n/a

allyl bromide (106-95-6) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
	4%

methanol (67-56-1) + 2-butenoic acid (3724-65-0) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With sulfuric acid
With hydrogenchloride
With sulfuric acid

2-butenoic acid (3724-65-0) + dimethylsulfite (616-42-2) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With mineral acid

tetramethylorthosilicate (681-84-5) + (E)-but-2-enoic acid (107-93-7) → crotonic acid methyl ester (623-43-8)

1,1-dimethoxyethylene (922-69-0) + acetaldehyde (75-07-0) → Trimethyl orthoacetate (1445-45-0) + trans-Crotonaldehyde (123-73-9) + crotonic acid methyl ester (623-43-8) + acetic acid methyl ester (79-20-9)

Conditions	Yield
at 150℃;

4-methyloxetan-2-one (3068-88-0, 32082-74-9, 36536-46-6, 65058-82-4) + methyl iodide (74-88-4) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With 18-crown-6 ether; potassium naphthalenide 1) THF, 20 deg C, 10 min; Yield given. Multistep reaction;

methanol (67-56-1) + trans-chrotonyl chloride (625-35-4, 3488-22-0, 10487-71-5) → crotonic acid methyl ester (623-43-8) + methyl but-3-enoate (3724-55-8)

Conditions	Yield
With 2,4-dimethylaminopyridine; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.5h; Yield given. Yields of byproduct given;

methanol (67-56-1) + 4,4-bis-methylsulfanyl-but-3-en-2-ol (15081-72-8) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With boron trifluoride diethyl etherate 1) room temp., 5 min, 2) reflux, 16 h; Yield given. Multistep reaction;

methanol (67-56-1) + 1-chloroethyl trans-crotonate (91488-52-7) → crotonic acid methyl ester (623-43-8)

Conditions	Yield
With toluene-4-sulfonic acid for 9h; Heating;	1.28 g

methanol (67-56-1) + 2-chloropropyl trans-crotonate → crotonic acid methyl ester (623-43-8)

glutaric anhydride, (108-55-4) → 3,4,5,6-tetrahydro-2H-pyran-2-one (542-28-9) + crotonic acid methyl ester (623-43-8) + butanoic acid methyl ester (623-42-7) + methyl but-3-enoate (3724-55-8) + methyl heptanoate (106-73-0) + dimethyl subarate (1732-09-8)

Conditions	Yield
With electrochemical reduction Product distribution; by-products;

nitromethane (75-52-5) + crotonic acid methyl ester (623-43-8) → methyl 3-methyl-4-nitro-butyrate (16507-06-5)

Conditions	Yield
With N,N,N',N'-tetramethylguanidine at 20℃; for 576h;	100%
With DBN In methanol at 60℃; for 6h; Inert atmosphere;	71.44%
With methanol; potassium carbonate
With N-benzyl-trimethylammonium hydroxide In methanol
With 1,8-diazabicyclo[5.4.0]undec-7-ene In methanol Michael addition;

crotonic acid methyl ester (623-43-8) → methyl 2,3-dibromobutyrate (5469-24-9)

Conditions	Yield
With bromine In dichloromethane at 0 - 20℃; Inert atmosphere;	100%
With bromine In acetic acid at 30℃; Mechanism; Rate constant;
With bromine
With bromine In tetrachloromethane at 0℃; for 0.5h;
With bromine In n-heptane at 25 - 35℃; for 1.33333 - 1.5h;

crotonic acid methyl ester (623-43-8) → butanoic acid methyl ester (623-42-7)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; methylcopper; diisobutylaluminium hydride In tetrahydrofuran; diethyl ether; hexane at -50℃; for 0.5h;	100%
With hydrogen; Rhodium chloride tri(triphenylphosphine-meta-trisulfonate) In water for 16h; Ambient temperature;	95%
With hydrogen; Pd(II) complex containing tridentate hydrazonic ligands In methanol at 40℃; for 24h; Hydrogenation;	35%
With hydrogen; montmorillonite-(bipyridine)x In benzene at 75℃; under 31028.9 Torr; for 45h;	91 % Spectr.
With hydrogen In methanol at 80℃; under 37503.8 Torr; for 20h; Autoclave;

piperidine (110-89-4) + crotonic acid methyl ester (623-43-8) → (+/-)-3-(1-piperidinyl)butyric acid methyl ester (122958-11-6)

Conditions	Yield
[(dppf)Pd(NCMe)(H2O)](OTf)2 In toluene at 20℃; for 18h;	100%
In methanol at 20℃; for 168h; Addition;	85%
With 3-butyl-1-methylimidazolium hydroxide at 25℃; for 1.5h; aza-Michael addition;	85%

crotonic acid methyl ester (623-43-8) + para-thiocresol (106-45-6) → 4-(4-mercapto-phenyl)-3-methyl-butyric acid methyl ester

Conditions	Yield
With magnesium oxide In toluene at 20℃; for 0.5h; Michael addition;	100%

crotonic acid methyl ester (623-43-8) → 5-methyl-pyrazolidin-3-one (10234-76-1)

Conditions	Yield
With hydrazine hydrate	100%

crotonic acid methyl ester (623-43-8) + benzyl-methyl-amine (103-67-3) → methyl 3-(N-benzyl-N-methylamino)-3-methylpropionate (40871-09-8)

Conditions	Yield
	100%
	100%
	100%
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 50℃; for 14h; aza-Michael addition;	77%

crotonic acid methyl ester (623-43-8) + methyl nonyl ketone (112-12-9) → 4,5-Dimethyl-5-nonyl-dihydro-furan-2-one (111748-84-6, 111748-88-0)

Conditions	Yield
With samarium diiodide; isopropyl alcohol In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at 0℃; for 0.0166667h;	99%

crotonic acid methyl ester (623-43-8) + 2-(Trimethylsilyl)benzenethiol (33356-45-5) → (S)-3-(2-Trimethylsilanyl-phenylsulfanyl)-butyric acid methyl ester

Conditions	Yield
With 2-TMSC6H4SLi; (-)-(1R,2R)-1-dimethylamino-2-(2-methoxyphenoxy)-1,2-diphenylethane In hexane; toluene at -78℃; for 120h; Addition;	99%

crotonic acid methyl ester (623-43-8) + benzylamine (100-46-9) → methyl 3-(benzylamino)butanoate (507444-65-7)

Conditions	Yield
In ethanol for 16h; Heating;	99%
In methanol at 150℃; under 5688.78 Torr; for 3h; Michael addition; microwave irradiation;	98%
In methanol at 20℃; for 2h;	96%

crotonic acid methyl ester (623-43-8) + N-(diphenylmethylene)glycine tert-butyl ester (81477-94-3) → 2-tert-butyl 4-methyl 3-methyl-5,5-diphenylpyrrolidine-2,4-dicarboxylate

Conditions	Yield
With 4 A molecular sieve; calcium bis-iso-propoxide; 2,2'-methylene bis((4S)-4-phenyl-2-oxazoline) In tetrahydrofuran at -30℃; for 12h; Michael addition;	99%

crotonic acid methyl ester (623-43-8) + 1H-4(5)-nitroimidazole (3034-38-6) → 3-(4-nitroimidazol-1-yl)-butyric acid methyl ester

Conditions	Yield
With 1-methyl-1H-imidazole In dimethyl sulfoxide at 70℃; for 12h; Michael addition;	99%
With acylase Amano from Aspergillus oryzae In dimethyl sulfoxide at 50℃; for 24h; Michael addition reaction;	37%

1-thiopropane (107-03-9) + crotonic acid methyl ester (623-43-8) → C8H16O2S + C8H16O2S

Conditions	Yield
With C49H53N4O4PS In toluene at 20℃; for 3h; Reagent/catalyst; enantioselective reaction;	A n/a B 99%

2-methylimidazole (693-98-1) + crotonic acid methyl ester (623-43-8) → methyl 3-(2-methyl-1H-imidazol-1-yl)butanoate

Conditions	Yield
In neat (no solvent) at 80℃; for 24h; Michael Addition; Schlenk technique; Sealed tube;	98.5%

crotonic acid methyl ester (623-43-8) + cyclohexanecarbaldehyde (2043-61-0) → 5-cyclohexyl-4-methyl-dihydrofuran-2(3H)-one

Conditions	Yield
With samarium diiodide In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; isopropyl alcohol for 0.0166667h;	98%

crotonic acid methyl ester (623-43-8) + guanidine hydrogen carbonate (124-46-9, 20734-13-8, 100224-74-6, 593-85-1) + malononitrile (109-77-3) → 2,4-diamino-5,6-dihydro-5-methylpyrido<2,3-d>pyrimidin-7(8H)-one (97934-10-6)

Conditions	Yield
Stage #1: guanidine hydrogen carbonate With sodium methylate In methanol for 0.25h; Heating; Stage #2: crotonic acid methyl ester; malononitrile In methanol at 140℃; for 0.166667h; Irradiation;	98%

crotonic acid methyl ester (623-43-8) + guanidine hydrogen carbonate (124-46-9, 20734-13-8, 100224-74-6, 593-85-1) + methyl 2-cyanoacetate (105-34-0) → 2-amino-4-hydroxy-5-methyl-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one

Conditions	Yield
Stage #1: guanidine hydrogen carbonate With sodium methylate In methanol for 0.25h; Heating; Stage #2: crotonic acid methyl ester; methyl 2-cyanoacetate In methanol at 140℃; for 0.166667h; Irradiation;	98%

(6-oxo-4-oxy-3,6-dihydro-2H-pyrazin-1-yl)-acetic acid methyl ester (930122-16-0) + crotonic acid methyl ester (623-43-8) → 5-methoxycarbonylmethyl-2-methyl-4-oxo-hexahydro-isoxazolo[2,3-a]pyrazine-3-carboxylic acid methyl ester

Conditions	Yield
With ytterbium(III) triflate In tetrahydrofuran for 14h; Heating;	98%

1-(N,N‑dimethylcarbamoyl)indole (70957-05-0) + crotonic acid methyl ester (623-43-8) → (E)-methyl 3-(1-(dimethylcarbamoyl)-1H-indol-2-yl)but-2-enoate (1454704-66-5)

Conditions	Yield
With tris(acetonitrile)(η5-pentamethylcyclopentadienyl)rhodium(III) hexafluoroantimonate; copper(II) acetate monohydrate In tetrahydrofuran at 100℃; for 24h; Heck Reaction; Inert atmosphere; stereoselective reaction;	98%
With silver hexafluoroantimonate; [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; copper(II) acetate monohydrate In 1,4-dioxane at 100℃; for 30h; Schlenk technique; Inert atmosphere; regioselective reaction;	90%

tert-butyl (S,E)-4-methyl-2-((thiazol-2-ylmethylene)amino)pentanoate + crotonic acid methyl ester (623-43-8) → 2-tert-butoxycarbonyl-2-isobutyl-4-methoxycarbonyl-3-methyl-5-thiazol-2-ylpyrrolidine

Conditions	Yield
With C34H43N4O6Zn(1+)*CF3O3S(1-) In acetonitrile at 50℃; for 24h; Schlenk technique; Inert atmosphere; enantioselective reaction;	98%

1H-imidazole (288-32-4) + crotonic acid methyl ester (623-43-8) → 3-imidazol-1-yl-butyric acid methyl ester (1153450-51-1)

Conditions	Yield
In neat (no solvent) at 80℃; for 24h; Michael Addition; Schlenk technique; Sealed tube;	97.5%

crotonic acid methyl ester (623-43-8) + benzaldehyde (100-52-7) → 5-hydroxy-5-phenyl-pent-2-enoic acid methyl ester (72853-47-5)

Conditions	Yield
Stage #1: crotonic acid methyl ester; benzaldehyde With aluminium tris(2,6-diphenylphenoxide) In toluene at -78℃; for 0.333333h; Complexation; Stage #2: With 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran; hexane; toluene at -78℃; for 0.5h; Crossed aldol condensation;	97%
Stage #1: crotonic acid methyl ester; benzaldehyde With aluminium tris(2,6-diphenylphenoxide) In toluene at -78℃; for 0.0833333h; Stage #2: With 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran; hexane; toluene at -78℃; for 0.5h;	97%
Stage #1: crotonic acid methyl ester; benzaldehyde With aluminum tris(2,6-di-2-naphthylphenoxide) In toluene at -78℃; for 0.333333h; Inert atmosphere; Stage #2: With 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran; toluene at -78℃; for 3h; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; toluene at -78 - 20℃; for 0.5h; Inert atmosphere;	97%

crotonic acid methyl ester (623-43-8) + C14H22N2O2S → 2-tert-butoxycarbonyl-2-isobutyl-4-methoxycarbonyl-3-methyl-5-thiazol-2-ylpyrrolidine

Conditions	Yield
With CF3O3S(1-)*C32H40N4O4*Zn(2+)*C2H3O2(1-) In acetonitrile at 80℃; for 60h; enantioselective reaction;	97%

crotonic acid methyl ester (623-43-8) + malonic acid dimethyl ester (108-59-8) → 2-methylpropan-1,1,3-tricarboxylic acid trimethyl ester (65844-74-8)

Conditions	Yield
Stage #1: malonic acid dimethyl ester With sodium methylate In tetrahydrofuran; methanol at 23℃; for 0.166667h; Stage #2: crotonic acid methyl ester In tetrahydrofuran; methanol at 45 - 50℃; for 4.16667h;	96%
With sodium methylate In methanol Heating;	84%

crotonic acid methyl ester (623-43-8) + cyclohexanecarbaldehyde (2043-61-0) → cis-(RS,SR)-γ-cyclohexyl-γ-hydroxy-β-methylbutanoic acid lactone (111748-83-5, 111748-87-9, 133101-54-9, 133101-64-1)

Conditions	Yield
With samarium diiodide; isopropyl alcohol In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide at 0℃; for 0.0166667h; Product distribution; without HMPA, further reaction time;	96%

crotonic acid methyl ester (623-43-8) → (Z) methyl 2-chloro-2-butenoate (22038-57-9, 60753-84-6, 22038-58-0)

Conditions	Yield
With aluminium trichloride; benzeneseleninyl chloride In dichloromethane at 40℃; for 23h;	96%
With chlorine In dichloromethane for 0.666667h;	34%
Multi-step reaction with 2 steps 1: Cl2 / CCl4 / 48 h / 0 °C 2: triethylamine / 72 h View Scheme
Multi-step reaction with 2 steps 1: Cl2, Br2 / CCl4 / 48 h / 0 °C 2: triethylamine / 72 h View Scheme

crotonic acid methyl ester (623-43-8) + (S)-1-(4-benzyl-2-oxazolidin-3-yl)propan-1-one → (S)-4-benzyl-3-(4-methoxycarbonyl-2,3-dimethylbutanoyl)oxazolidine

Conditions	Yield
With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; for 1h;	96%

crotonic acid methyl ester (623-43-8) + (5R)-5,6-dihydro-5-phenyl-2H-1,4-oxazin-2-one-N-oxide (182316-01-4) → (2R,6R,7R,8S)-2-phenyl-8-methyl-1-aza-4,9-dioxa[4.3.0]bicyclononan-5-one-7-carboxylic acid, methyl ester

Conditions	Yield
In chloroform for 3h; Ambient temperature;	96%

crotonic acid methyl ester (623-43-8) + cyclohexanecarbaldehyde (2043-61-0) → (E)-methyl 5-cyclohexyl-5-hydroxypent-2-enoate

Conditions	Yield
Stage #1: crotonic acid methyl ester; cyclohexanecarbaldehyde With aluminum tris(2,6-di-2-naphthylphenoxide) In toluene at -78℃; for 0.333333h; Inert atmosphere; Stage #2: With 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran; toluene at -78℃; for 3h; Inert atmosphere; Stage #3: With ammonium chloride In tetrahydrofuran; toluene at -78 - 20℃; for 0.5h; Inert atmosphere;	96%
Stage #1: crotonic acid methyl ester; cyclohexanecarbaldehyde With aluminium tris(2,6-diphenylphenoxide) In toluene at -78℃; for 0.333333h; Complexation; Stage #2: With 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran; hexane; toluene at -78℃; for 0.5h; Crossed aldol condensation;	90%

crotonic acid methyl ester (623-43-8) + benzaldehyde (100-52-7) → Methyl 4-benzoylbutanoate (1501-04-8)

Conditions	Yield
With 3-methylpyridin-2-ylamine; benzoic acid; Wilkinson's catalyst In toluene at 150℃; for 72h;	96%

Upstream product

• 3068-88-0 4-methyloxetan-2-one 
• 865-33-8 potassium methanolate 
• 75-03-6 ethyl iodide 
• 74-88-4 methyl iodide 
• 67-56-1 methanol 
• 201230-82-2 carbon monoxide 
• 107-05-1 3-chloroprop-1-ene 
• 1117-71-1 methyl-4-bromo-2-butenoate 
• 100-52-7 benzaldehyde 
• 71-43-2 benzene 
• 616-42-2 dimethylsulfite 
• 107-93-7 (E)-but-2-enoic acid 
• 78-40-0 triethyl phosphate 
• 816-11-5 2-ethyl-butyric acid methyl ester 

Downstream Products

• 92-92-2 biphenyl-4-carboxylic acid 
• 10024-70-1 3-methoxybutanoic acid 
• 1117-71-1 methyl-4-bromo-2-butenoate 
• 595-41-5 2,3-dimethyl-3-pentanol 
• 858782-46-4 2-chloro-3-(2,4-dichloro-phenyl)-butyric acid methyl ester 
• 854647-23-7 3-chloro-2-(2,4-dichloro-phenyl)-butyric acid methyl ester 
• 91956-99-9 methyl 4-cyano-3-methyl-4-phenylbutanoate 
• 73326-70-2 4-((1R,2S)-2-Methoxy-cyclohexyl)-3-methyl-butyric acid methyl ester 
• 26708-31-6 erythro-methyl 2,3-dichlorobutanoate 
• 77332-69-5 erythro-methyl 3-chloro-2-methoxybutanoate 
• 26839-90-7 erythro-methyl 2-chloro-3-methoxybutanoate 
• 125506-33-4 3-(Benzhydrylidene-amino)-butyric acid methyl ester 
• 112545-19-4 (R)-3-Methyl-2-((R)-1-phenyl-ethyl)-isoxazolidin-5-one 
• 112692-05-4 (S)-3-Methyl-2-((R)-1-phenyl-ethyl)-isoxazolidin-5-one 

Relevant articles and documents

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