1068-90-2

Basic information

• Product Name: Diethyl acetamidomalonate
• Synonyms: PROPANEDIOIC ACID, (ACETYLAMINO)-, DIETHYL ESTER;(Acetylamino)propanedioic acid diethyl ester;(acetylamino)-propanedioicacidiethylester;2-(Acetylamino)propanedioic acid diethyl ester;acetamido-malonicacidiethylester;Acetaminomalonic acid diethyl ester;Acetaminomalonicaciddiethylester;Diethyl 2-(acetylamino)malonate
• CAS NO: 1068-90-2
• Molecular Formula: C₉H₁₅NO₅
• Molecular Weight: 217.22
• EINECS: 213-952-9
• Product Categories: Pharmaceutical Intermediates;Other Reagents;Amino ester;ester series;Building Blocks;C8 to C9;Carbonyl Compounds;Chemical Synthesis;Esters;Organic Building Blocks;Pyridines
• Mol File: 1068-90-2.mol
• Article Data: 15

Chemical Properties

• Melting Point: 95-98 °C(lit.)
• Boiling Point: 185 °C20 mm Hg(lit.)
• Flash Point: 185°C/20mm
• Appearance: White to light yellow/Crystalline Powder
• Density: 1.2850 (rough estimate)
• Vapor Pressure: 0.000565mmHg at 25°C
• Refractive Index: 1.4640 (estimate)
• Storage Temp.: Store at RT.
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 11.93±0.59(Predicted)
• Water Solubility: Soluble in chloroform and methanol. Slightly soluble in water.
• BRN: 783883
• CAS DataBase Reference: Diethyl acetamidomalonate(CAS DataBase Reference)
• NIST Chemistry Reference: Diethyl acetamidomalonate(1068-90-2)
• EPA Substance Registry System: Diethyl acetamidomalonate(1068-90-2)

Safety Data

• Hazard Codes: Xi
• Statements: 36-36/37/38
• Safety Statements: 39-36-26-44
• WGK Germany: 3
• RTECS: OO0360000
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 1068-90-2(Hazardous Substances Data)

Usage

Chemical Properties

white to light yellow crystalline powder

Uses

Diethyl 2-Acetamidomalonate, is a versatile building block used for the synthesis of various pharmaceutical and biologically active compounds. It is an intermediate for the preparation of Novobiocin analogues as potential heat shock protein 90 inhibitors. It is also used as a important intermediates in syntheses of vitamins B1 and B6, barbiturates, non-steroidal anti-inflammatory agents, other numerous pharmaceuticals.

Safety Profile

An eye irritant. When heated todecomposition it emits toxic fumes of NOx.

Purification Methods

Crystallise the ester from *benzene/pet ether. [Beilstein 4 III 2993.]

InChI:InChI=1/C9H15NO5/c1-4-14-8(12)7(10-6(3)11)9(13)15-5-2/h7H,4-5H2,1-3H3,(H,10,11)

Synthetic route

diethyl aminomalonate hydrochloride (13433-00-6) + acetic anhydride (108-24-7) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	100%
With triethylamine In dichloromethane at 0 - 20℃;	99%

diethyl 2-aminopropanedioate hydrochloride + acetic anhydride (108-24-7) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

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

diethyl aminomalonate hydrochloride (13433-00-6) + acetyl chloride (75-36-5) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	96%
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	96%

diethyl 2-aminopropanedioate hydrochloride + acetyl chloride (75-36-5) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 20℃;	96%

acetamide (60-35-5) + diethyl malonate (105-53-3) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With 2,2′-biquinoline-4,4'-dicarboxylic acid disodium salt; acetic acid; copper(l) chloride at 80 - 110℃; for 8h;	93%

diethyl oximinomalonate (6829-41-0) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With zinc In water	90%
Multi-step reaction with 2 steps 1: H2 / 10percent Pd/C / ethanol / 20520 Torr 2: ethanol View Scheme
Multi-step reaction with 2 steps 1: palladium coal; ethanol / 2280 - 3040 Torr / Hydrogenation 2: ethanol View Scheme

acetic acid (64-19-7) + diethyl malonate (105-53-3) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With sodium nitrite Addition; Isonitrosoylation; N-acetylation;	87%

aminomalonic acid diethyl ester (6829-40-9) + Triethyl orthoacetate (78-39-7) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
for 2h; Reflux;	87%

diethyl malonate (105-53-3) → 1,4-dioxane (123-91-1) + 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With acetic acid; sodium nitrite In water	A n/a B 86%

diethyl acetylmalonate (570-08-1) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With chloroform; tris-(2-chloro-ethyl)-amine; sulfuric acid

diethyl acetylmalonate (570-08-1) → methylcarbamoyl-malonic acid diethyl ester (15129-21-2) + 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With hydrogen azide; chloroform; sulfuric acid
With sodium azide; chloroform; sulfuric acid

aminomalonic acid diethyl ester (6829-40-9) + acetic anhydride (108-24-7) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With ethanol
With pyridine
In ethanol Yield given;
With triethylamine In tetrahydrofuran at 23℃; for 1h;

diethyl oximinomalonate (6829-41-0) + acetic anhydride (108-24-7) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With nickel
With acetic acid; zinc

diethyl nitromalonate (603-67-8) + acetic anhydride (108-24-7) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With nickel Hydrogenation;
With palladium on activated charcoal at 60℃; under 58840.6 Torr; Hydrogenation;

acetic anhydride (108-24-7) + α-Benzolazo-malonsaeure-diethylester (13636-61-8) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With acetic acid; zinc

(1-ethoxy-ethylidenamino)-malonic acid diethyl ester + acetic acid (64-19-7) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
beim Kochen der Kalium-Verbindung;

aminomalonic acid diethyl ester (6829-40-9) + acetyl chloride (75-36-5) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With pyridine
With sodium carbonate In dichloromethane; water for 2h; Acetylation;
With benzothiazole-2-sulphonic acid In diethyl ether at 0 - 25℃; for 1h;

methanol (67-56-1) + ethene (74-85-1) + carbon monoxide (201230-82-2) + sodium diethyl (acetylamino)malonate (30412-43-2) → 1-acetamidopropanetricarboxylic acid 1,1-diethyl-3-methyl ester (74090-40-7) + 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
Yield given. Multistep reaction. Yields of byproduct given;

acetylamino-bromomethyl-malonic acid diethyl ester (91011-83-5) → diethyl 2-acetylaminobutanedioate (1069-38-1) + diethyl α-acetamido, α-methylmalonate (55166-91-1) + 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
carbon-skeleton rearrangement mediated by hydrophobic Vitamin B12 covalent bound to a lipid species in a bilayer membrane; 1.) NaBH4, complex 1, 2.) N,N-bis(hexadecyl)-Nα-(6-sulfohexanoyl)-L-alaninamide, irradiation; other medium for irradiation;	A 2 % Chromat. B 57 % Chromat. C 25 % Chromat.

acetylhydroxyimino-malonic acid diethyl ester → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With diethyl ether; aluminium amalgam

acetyl chloride (75-36-5) + sodium compound of aminomalonic acid diethyl ester → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
With pyridine

acetoxyimino-malonic acid diethyl ester (90713-04-5) + amalgamated aluminium → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
Reduktion;

diethyl malonate (105-53-3) + Me3SiCH2C(Me)=CH(CH2)2CH(Me)-X → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaH / tetrahydrofuran / 0.25 h / 23 °C 1.2: O-(4-nitrobenzoyl)-hydroxylamine / tetrahydrofuran / 23 °C 2.1: Et3N / tetrahydrofuran / 1 h / 23 °C View Scheme

ethylesters of amino malonic acid (91469-69-1) → 2-acetylaminomalonic acid diethyl ester (1068-90-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water / 5 h / Reflux 2: 2 h / Reflux View Scheme

benzyl chloride (100-44-7) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-(N-acetylamino)-2-benzylpropanedioic diethyl ester (3235-26-5)

Conditions	Yield
With 18-crown-6 ether; potassium carbonate In dichloromethane at 100 - 110℃; for 0.8h; Product distribution; var. solvents, var. time, other reaction partners;	100%
With 18-crown-6 ether; potassium carbonate In N,N-dimethyl-formamide at 100 - 110℃; for 0.8h;	100%
With ethanol; sodium ethanolate
With ethanol; sodium ethanolate

allyl bromide (106-95-6) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → ethyl 2-acetamido-2-(ethoxycarbonyl)-4-pentenoate (14109-62-7)

Conditions	Yield
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium ethanolate In ethanol for 5h; Reflux; Stage #2: allyl bromide In ethanol for 15h; Reflux;	100%
With caesium carbonate In acetonitrile Heating;	99%
With ethanol; sodium	97%

propargyl bromide (106-96-7) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl α-acetamido-α-propargylmalonate (61172-60-9)

Conditions	Yield
With caesium carbonate In acetonitrile at 20℃; for 18h;	100%
With caesium carbonate In acetonitrile at 20℃; for 18h;	99%
With sodium hydride In N,N-dimethyl-formamide at 60℃; for 3h;	95%

methyl chloroacetate (96-34-4) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-Acetylamino-2-ethoxycarbonyl-succinic acid 1-ethyl ester 4-methyl ester

Conditions	Yield
With 18-crown-6 ether; potassium carbonate In N,N-dimethyl-formamide at 100 - 110℃; for 0.5h;	100%

diethyl 2-bromoethylphosphonate (5324-30-1) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → (N-acetylamino-3 bis-ethoxycarbonyl-3,3)-propylphosphonate de diethyle (107257-47-6)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile for 8h; Heating;	100%
With sodium hydride In toluene at 110℃; for 24h;	100%
With sodium hydride; Diethyl carbonate In hexane; toluene; mineral oil at 110℃; for 24h;	33.3 g

bis(2-chloroethyl) 2-chloroethylphosphonate (6294-34-4) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → (N-acetylamino-3 bis-ethoxycarbonyl-3,3)-propylphosphonate de di(chloro-2 ethyle)

Conditions	Yield
With N-benzyl-N,N,N-triethylammonium chloride; potassium carbonate In acetonitrile for 8h; Heating;	100%

4-bromo-1-(bromomethyl)-2-nitrobenzene (82420-34-6) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → Ethyl 2-Acetamido-2-(4'-bromo-2'-nitrobenzyl)malonate (82420-36-8)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide	100%
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium ethanolate In ethanol at 20℃; for 0.5h; Stage #2: 4-bromo-1-(bromomethyl)-2-nitrobenzene In ethanol	74%
	68%

4-(bromomethyl)-1-fluoro-2-nitrobenzene (15017-52-4) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → ethyl 2-(acetylamino)-2-(ethoxycarbonyl)-3-(4'-fluoro-3'-nitrophenyl)propanoate (20367-99-1)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide for 4h; Ambient temperature;	100%
With sodium hydride In N,N-dimethyl-formamide; mineral oil; pentane at 20℃; for 4h;	100%
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium hydride In tetrahydrofuran; mineral oil for 3h; Reflux; Stage #2: 4-(bromomethyl)-1-fluoro-2-nitrobenzene In tetrahydrofuran; N,N-dimethyl-formamide; mineral oil Reflux;	100%
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium hydride In N,N-dimethyl-formamide; mineral oil Stage #2: 4-(bromomethyl)-1-fluoro-2-nitrobenzene In N,N-dimethyl-formamide; mineral oil at 20℃; for 24h;	74%
With sodium hydride In hexanes; N,N-dimethyl-formamide; mineral oil at 20℃; for 4h;

2-acetylaminomalonic acid diethyl ester (1068-90-2) + 6'-(bromomethyl)-3',4'-dihydro-4,4-dimethyl-7'-nitrospiro(cyclohexane-1,1'(2H)-naphthalene) (205386-16-9) → C27H38N2O7 (205386-17-0)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide for 2.5h; Ambient temperature;	100%

2-acetylaminomalonic acid diethyl ester (1068-90-2) + (4-methoxyphenyl)methyl methyl carbonate (270921-39-6) → 2-acetylamino-2-(4-methoxybenzyl)malonic acid diethyl ester (53612-87-6)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; N,O-bis-(trimethylsilyl)-acetamide; {(η4-1,5-cyclooctadiene)Pd(η3-allyl)}BF4; potassium acetate In tetrahydrofuran at 80℃; for 24h;	100%
With 1,1'-bis(diisopropylphosphino)ferrocene; {(η4-1,5-cyclooctadiene)Pd(η3-allyl)}BF4; caesium carbonate In N,N-dimethyl-formamide at 30℃; for 72h; Inert atmosphere;	95%
With 1,1'-bis-(diphenylphosphino)ferrocene; 1,5-cis,cis-cyclooctadiene; [PdCp(η3-C3H5)] In tetrahydrofuran at 80℃;	92%

2-isopropyl-4-chloromethylthiazole (40516-57-2) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl 2-acetamido-2-((2-isopropylthiazol-4-yl)methyl)malonate (1187649-36-0)

Conditions	Yield
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; Stage #2: 2-isopropyl-4-chloromethylthiazole In N,N-dimethyl-formamide at 20℃;	100%

formaldehyd (50-00-0) + benzyl-methyl-amine (103-67-3) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → C18H26N2O5

Conditions	Yield
In water at 20℃; for 4h;	100%

3-(Dimethylaminomethyl)indole (87-52-5) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → acetylamino-indol-3-ylmethyl-malonic acid diethyl ester (5379-97-5)

Conditions	Yield
With tributylphosphine In acetonitrile for 4h; Heating;	99.5%
With sodium hydroxide; toluene
With sodium hydroxide; xylene
With sodium ethanolate; ethyl iodide
With ethanol; dimethyl sulfate

[1-(5-bromomethyl-isoxazol-3-yl)-3-methyl-butyl]-carbamic acid tert-butyl ester + N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-acetylamino-2-[3-(1-tert-butoxycarbonylamino-3-methyl-butyl)-isoxazol-5-ylmethyl]-malonic acid diethyl ester

Conditions	Yield
With caesium carbonate	99.4%

4-Fluorobenzyl bromide (459-46-1) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl α-acetamido, α-(4-fluorobenzyl)malonate (380-71-2)

Conditions	Yield
With potassium carbonate In acetonitrile Alkylation; Heating;	99%
With potassium hydroxide; Aliquat 336 for 0.25h; Ambient temperature;	71%
With caesium carbonate In acetonitrile at 130℃; Microwave irradiation;

propargyl p-toluenesulfonate (6165-76-0) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl α-acetamido-α-propargylmalonate (61172-60-9)

Conditions	Yield
Stage #1: 2-acetylaminomalonic acid diethyl ester With potassium tert-butylate In 1,4-dioxane at 20 - 50℃; for 4h; Inert atmosphere; Stage #2: propargyl p-toluenesulfonate In 1,4-dioxane at 50℃; Concentration; Solvent; Inert atmosphere; Reflux;	99%

{4-(bromomethyl)-2-[(2-nitrobenzyl)oxy]phenoxy}(tert-butyl)dimethylsilane + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl 2-acetamido-2-{4-[(tert-butyldimethylsilyl)oxy]-3-[(2-nitrobenzyl)oxy]benzyl}malonate

Conditions	Yield
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.333333h; Inert atmosphere; Stage #2: {4-(bromomethyl)-2-[(2-nitrobenzyl)oxy]phenoxy}(tert-butyl)dimethylsilane In N,N-dimethyl-formamide; mineral oil at 20℃; for 4h; Inert atmosphere;	99%

4-bromomethyl-2(1H)-quinolinone (4876-10-2) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-acetylamino-2-(ethoxycarbonyl)-3-(2-oxo-1,2-dihydroquinolin-4-yl)propionic acid ethyl ester (4900-38-3)

Conditions	Yield
With sodium ethanolate; tetra-(n-butyl)ammonium iodide In ethanol at 60℃; for 8h; Reagent/catalyst; Temperature;	98.44%
With sodium In ethanol for 2h;	69%
With sodium hydroxide In water; dimethyl sulfoxide at 20 - 30℃; for 2h; Reagent/catalyst; Solvent; Large scale;

5-methoxygramine (16620-52-3) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → acetylamino-(5-methoxy-indol-3-ylmethyl)-malonic acid diethyl ester (54744-69-3)

Conditions	Yield
With sodium hydroxide In toluene for 18h; Reflux;	98%
With ethanol; sodium ethanolate; dimethyl sulfate

1-bromomethyl-3-nitrobenzene (3958-57-4) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl 2-(acetylamino)-2-(3-nitrobenzyl)malonate (5432-19-9)

Conditions	Yield
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: 1-bromomethyl-3-nitrobenzene In N,N-dimethyl-formamide; mineral oil at 0℃; for 16h; Inert atmosphere;	98%
With ethanol; sodium ethanolate

2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-acetamido-3-ethoxy-3-oxopropanoic acid (54681-67-3, 187868-53-7)

Conditions	Yield
With sodium hydroxide; phosphate buffer; α-chymotrypsin for 5.25h; Product distribution; Ambient temperature; var. pH;	98%
With sodium hydroxide In 1,4-dioxane; water at 20℃; for 17h;	81%
With sodium hydroxide In 1,4-dioxane at 20℃; for 15h;	76%

1-Bromo-3-phenylpropane (637-59-2) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-acetylamino-2-(3-phenyl-propyl)malonic acid diethyl ester (52161-73-6)

Conditions	Yield
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium ethanolate In ethanol at 20℃; for 1.5h; Stage #2: 1-Bromo-3-phenylpropane In ethanol for 16h; Heating;	98%
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium ethanolate In ethanol at 20℃; for 1.5h; Stage #2: 1-Bromo-3-phenylpropane In ethanol for 16.25h; Heating / reflux;	98%
(i) Na, EtOH, (ii) /BRN= 2205527/; Multistep reaction;
With sodium ethanolate; sodium In ethanol; nitrogen
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium ethanolate In ethanol at 20℃; for 2h; Stage #2: 1-Bromo-3-phenylpropane In ethanol at 20 - 73℃; for 28.25h;

benzyl bromide (100-39-0) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → 2-(N-acetylamino)-2-benzylpropanedioic diethyl ester (3235-26-5)

Conditions	Yield
With potassium carbonate In acetonitrile Alkylation; Heating;	98%
With potassium hydroxide; Aliquat 336 for 0.25h; Ambient temperature;	84%
With caesium carbonate In acetonitrile at 130℃; for 0.166667h; Microwave irradiation;	82%
Stage #1: 2-acetylaminomalonic acid diethyl ester With sodium ethanolate In ethanol at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: benzyl bromide In ethanol for 2h; Inert atmosphere; Reflux;
With caesium carbonate In acetonitrile at 130℃; Microwave irradiation;

rac-(E)-1,3-diphenyl-3-acetoxy-prop-1-ene (87751-69-7) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl (R)-(acetylamino)[(E)-1,3-diphenylprop-2-en-1-yl]malonate

Conditions	Yield
With N,O-bis-(trimethylsilyl)-acetamide; potassium acetate; chiral (phosphinoaryldihydrooxazole)allyl-Pd(II) In dichloromethane at 23℃;	98%
With bis(η3-allyl-μ-chloropalladium(II)); C2-symmetric chiral P; potassium acetate; bis-(trimethylsilyl)acetamide In dichloromethane for 0.5h; Ambient temperature;	98%

4-(bromomethyl)-3-nitrobenzaldehyde (155526-65-1) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → ethyl 2-(acetylamino)-2-(ethoxycarbonyl)-3-(4-formyl-2-nitrophenyl)propanoate (168965-43-3)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide for 2.5h; Ambient temperature;	98%
With sodium hydride In N,N-dimethyl-formamide

rac-(E)-1,3-diphenyl-3-acetoxy-prop-1-ene (87751-69-7) + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl (S)-(acetylamino)[(E)-1,3-diphenylprop-2-en-1-yl]malonate

Conditions	Yield
With N,O-bis-(trimethylsilyl)-acetamide; bis(η3-allyl-μ-chloropalladium(II)); (S)-7-(diphenylphosphino)-2′-isopropyl-2,3-dihydro-5′H-spiro[indene-1,4′-oxazole]; potassium acetate In toluene at 0℃; for 5h; Inert atmosphere; Schlenk technique; enantioselective reaction;	98%
With bis(η3-allyl-μ-chloropalladium(II)); potassium acetate; (1R,2R)-2-[N-(2-diphenylphosphanylbenzoyl)amino]cyclohexylcarbamic acid tert-butyl ester In diethyl ether at 25℃; for 6h; enantioselective reaction;	98%
With benzenesulfonamide; potassium acetate; (1R,2S,4R,5S)-(+)-2,5-dimethyl-7-phenyl-7-phosphabicyclo[2.2.1]heptane; bis(η3-allyl-μ-chloropalladium(II)) In toluene for 2h;	95%
With benzenesulfonamide; potassium acetate; (S,S)-N,N'-1,2-bis(S-cyclopentyl-S-phenyl-sulfonimidoyl)-ethane; bis(η3-allyl-μ-chloropalladium(II)) In dichloromethane at 45℃; for 96h;	89%

2-acetylaminomalonic acid diethyl ester (1068-90-2) + 2-ethylsulfanyl-3-(ethylsulfanyl-trimethylsilanyl-methyl)-1H-indole (247222-86-2) → 2-acetylamino-2-(2-ethylsulfanyl-1H-indol-3-ylmethyl)-malonic acid diethyl ester

Conditions	Yield
With tributylphosphine In acetonitrile at 80℃; for 9h; Alkylation;	98%

methyl (naphthalen-1-ylmethyl) carbonate + 2-acetylaminomalonic acid diethyl ester (1068-90-2) → diethyl (N-acetylamino)[(1-naphthyl)methyl]malonate (5440-57-3)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; [PdCp(η3-C3H5)] In tetrahydrofuran at 80℃; for 1h;	98%

Upstream product

• 6829-40-9 aminomalonic acid diethyl ester 
• 108-24-7 acetic anhydride 
• 64-19-7 acetic acid 
• 75-36-5 acetyl chloride 
• 105-53-3 diethyl malonate 
• 60-35-5 acetamide 
• 91469-69-1 ethylesters of amino malonic acid 
• 78-39-7 Triethyl orthoacetate 
• 13433-00-6 diethyl aminomalonate hydrochloride 
• 6829-41-0 diethyl oximinomalonate 
• 90713-04-5 acetoxyimino-malonic acid diethyl ester 
• 91011-83-5 acetylamino-bromomethyl-malonic acid diethyl ester 
• 67-56-1 methanol 
• 74-85-1 ethene 

Downstream Products

• 54744-69-3 acetylamino-(5-methoxy-indol-3-ylmethyl)-malonic acid diethyl ester 
• 5440-50-6 N-acetyl-3-(2-chlorophenyl)-2-ethoxycarbonyl alanine ethyl ester 
• 101288-14-6 acetylamino-benzoyl-malonic acid diethyl ester 
• 150722-71-7 acetylamino-(3-phenoxy-propyl)-malonic acid diethyl ester 
• 168154-47-0 acetylamino-(3-methoxy-phenacyl)-malonic acid diethyl ester 
• 5440-42-6 ethyl 2-acetamido-4-cyano-2-ethoxycarbonylbutanoate 
• 57746-21-1 acetylamino-(3-oxo-1-phenyl-propyl)-malonic acid diethyl ester 
• 6941-36-2 2-acetylamino-2-(4-chlorobenzyl)malonic acid diethyl ester 
• 5440-53-9 2-acetylamino-2-(2-methylbenzyl)malonic acid diethyl ester 
• 50469-23-3 acetylamino-(5-benzyloxy-indol-3-ylmethyl)-malonic acid diethyl ester 
• 5432-19-9 diethyl 2-(acetylamino)-2-(3-nitrobenzyl)malonate 
• 6265-87-8 2-acetylamino-2-(4-nitrobenzyl)malonic acid diethyl ester 
• 102953-09-3 3,3-Dibenzoyl-1,1-bis-carbaethoxy-1-acetamino-propan 
• 101782-54-1 Acetamino-cinnamyl-malonsaeure-diethylester 

Relevant articles and documents

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Improved Reagent for Electrophilic Amination of Stabilized Carbanions

(Equation presented) Enolate amination using O-di(p-methoxyphenyl) phosphinylhydroxylamine 2 is reported. Reagent 2 reacts efficiently with stabilized sodium or potassium enolates derived from malonates, phenylacetates, and phenylacetonitriles and is sufficiently soluble for use in solution at -78°C.

Synthetic method of diethyl acetyl malonate

The invention discloses a synthetic method for diethyl acetamidomalonate. The method comprises the following steps: firstly, performing a reaction in the presence of a metal salt and a ligand to prepare a mixed liquid containing the diethyl acetamidomalonate by taking diethyl malonate and acetamide as raw materials, air as an oxidant, and acetic acid as a solvent, performing distilling, and performing repeated extraction and recrystallization to obtain the diethyl acetamidomalonate in a white crystalline powder state. The method has the advantages that the metal salt and the ligand are cheap and easy to obtain, after the reaction is finished, the metal salt and the ligand can be further recycled through treatment, the air is taken as the oxidant, and therefore the production costs are greatly reduced; the yield of the product is more than 90%, the purity of the product is more than 99%, the conversion rates of the raw materials are high, and the reaction is complete; and the by-productis only water, no ''three waste'' (waste gas, waste water and solid waste) pollution problems exist, and the method meets environmental protection requirements.

NEW LIGANDS FOR TARGETING OF S1P RECEPTORS FOR IN VIVO IMAGING AND TREATMENT OF DISEASES

The present invention relates to novel compounds of formulae (I) and (II) which are useful in the prevention, treatment and diagnosis, in vivo diagnosis of diseases or disorders related to S1P receptors, in particular, in diseases which are connected to the regulatory function of sphingosine-1-phosphate (S1P) and its analogues, such as inflammation, pain, autoimmune diseases and cardiovascular diseases.