2999-46-4

Basic information

• Product Name: Ethyl isocyanoacetate
• Synonyms: Ethylisocyanoacetate,98%;Acetic acid, isocyano-, ethyl ester;(2-Oxo-2-ethoxyethyl) isocyanide;2-Oxo-2-ethoxyethyl isocyanide;Ethoxycarbonylmethyl isocyanide;Ethyl 2-isocyanoacetate;Ethyl isocyanoacetate,97%;Ethyl isocyanoacetate,99+%
• CAS NO: 2999-46-4
• Molecular Formula: C₅H₇NO₂
• Molecular Weight: 113.11
• EINECS: 221-077-9
• Product Categories: straight chain compounds;pharmacetical;Naphthyridine,Quinoline;Isocyanides;Nitrogen Compounds;Organic Building Blocks;fine chemicals, specialty chemicals, intermediates, electronic chemical, organic synthesis;Building Blocks;Chemical Synthesis;Nitrogen Compounds;Organic Building Blocks
• Mol File: 2999-46-4.mol
• Article Data: 25

Chemical Properties

• Boiling Point: 194-196 °C(lit.)
• Flash Point: 184 °F
• Appearance: Clear amber to dark brown/Liquid
• Density: 1.035 g/mL at 25 °C(lit.)
• Vapor Pressure: 61.7Pa at 25℃
• Refractive Index: n20/D 1.418(lit.)
• Storage Temp.: 2-8°C
• Water Solubility: Miscible with organic solvents. Slightly miscible with water.
• Sensitive: Moisture & Light Sensitive
• BRN: 3588613
• CAS DataBase Reference: Ethyl isocyanoacetate(CAS DataBase Reference)
• NIST Chemistry Reference: Ethyl isocyanoacetate(2999-46-4)
• EPA Substance Registry System: Ethyl isocyanoacetate(2999-46-4)

Safety Data

• Hazard Codes: Xn
• Statements: 20/22-20/21/22
• Safety Statements: 36/37/39-26-36/37-24/25
• RIDADR: UN 2810 6.1/PG 3
• WGK Germany: 3
• F: 8-9-21
• HazardClass: 6.1
• PackingGroup: III
• Hazardous Substances Data: 2999-46-4(Hazardous Substances Data)

Usage

Chemical Properties

Light yellow to brom liquid. Slightly soluble in water and lye, miscible in ethanol and ether.

Uses

Different sources of media describe the Uses of 2999-46-4 differently. You can refer to the following data:
1. Ethyl Isocyanoacetate, is a cyclization synthon used to prepare pyrroles, oxazolines, benzodiazepines, oxazoles and imidazoles. Ethyl isocyanoacetate can be used to prepare pyrroles,1,2 oxazolines, benzodiazepines, oxazoles and imidazoles.
2. Ethyl isocyanoacetate is used in the syntheses of 7-aza-tetrahydroindoles, oxazolines, benzodiazepines, imidazoles and oxazoles. For example, it is involved in the synthesis of 1H-indole-2-carboxylate by condensing with 2-bromo benzenealdehyde using CuI as a catalyst. It is a precursor used in the preparation of ethyl thiazole-4-carboxylate upon reaction with O-ethyl thioformate.

Preparation

synthesis of ethyl isocyanoacetate A solution containing N-formyl glycine ethyl ester (1, 1.31 g, 10 mmol), DIPEA (2.62 g, 20 mmol) and DMAP (0.45 g, 3 mmol) in dry DCM (10 mL) was loaded in a sample loop and combined with a second stream containing triphosgene (2, 0.98 g, 3.3 mmol) also dissolved in dry DCM (10 mL) at individual channel flow rates of 0.5 mL/min. The combined stream was directed into two linked 10 mL FEP reactor vessels to achieve a 20 minutes residence time at ambient temperature. The output was collect and the solvent was carefully evaporated to 80% of its total volume. The crude material was filtered through silica (5 g) and washed with DCM (2 × 10 mL) to obtain the salt-free product. The desired product 3 was obtained as dark yellow oil after evaporation of the organic phase (1.03 g, 91 % isolated yield, >97% purity by 1H NMR).

General Description

Material may darken upon storage

InChI:InChI=1/C5H7NO2/c1-3-4(6-2)5(7)8/h4H,3H2,1H3,(H,7,8)/p-1

Upstream product

• 2491-15-8 formylglycine 
• 623-33-6 glycine ethyl ester hydrochloride 
• 109-94-4 formic acid ethyl ester 
• 58948-98-4 potassium 2-isocyanoacetate 
• 3154-51-6 ethyl N-formylglycinate 
• 56-40-6 glycine 
• 459-73-4 GlyOEt*HCl 
• 593-75-9 methyl isocyanate 
• 105-58-8 Diethyl carbonate 

Downstream Products

• 62640-98-6 5-(D_r-1c_F,2t_F,3c_F,5-tetrakis-benzyloxy-4r_F-hydroxy-pent-cat_F-yl)-oxazole-4-carboxylic acid ethyl ester 
• 66107-90-2 5-(D_r-1c_F,2t_F,3c_F,5-tetrakis-benzyloxy-4r_F-hydroxy-pent-cat_F-yl)-oxazole-4-carboxylic acid benzyl ester 
• 7298-97-7 β-Ethyl-DL-asparaginsaeure 
• 72030-87-6 5-(4-nitrophenyl)oxazole-4-carboxylic acid ethyl ester 
• 61323-29-3 ethyl 5-benzylthiazole-4-carboxylate 
• 124731-73-3 (+)-N-glycyl>-L*-prolyl>glycine ethyl ester 
• 124731-73-3 (+)-N-glycyl>-L*-prolyl>glycine ethyl ester 
• 114629-44-6 2-diacetylmethylen-1-(ethoxycarbonylmethylimino)-3,4-diphenylcyclobuten 
• 114629-69-5 4-dicyanomethylen-3-ethoxycarbonyl-1-ethoxycarbonylmethyl-5,6-diphenylcyclopent-5-en<2.3-b>imidazole 
• 126760-77-8 3-(2-Methoxy-phenyl)-4-methyl-1H-pyrrole-2-carboxylic acid ethyl ester 
• 21390-88-5 ethyl 3-phenyl-1H-pyrrole-2-carboxylate 
• 100780-40-3 Ethyl 3-(p-benzyloxy-phenyl)-4-methylpyrrole-2-carboxylate 
• 93911-40-1 Benzoic acid 2-chloro-1-chloromethyl-1-(ethoxycarbonylmethyl-carbamoyl)-ethyl ester 
• 124731-75-5 (+)-N-glycine ethyl ester 

Relevant articles and documents

Dispirooxindoles based on 2-selenoxo-imidazolidin-4-ones: Synthesis, cytotoxicity and ros generation ability

A regio-and diastereoselective synthesis of two types of dispiro derivatives of 2-selenoxoim-idazolidin-4-ones, differing in the position of the nitrogen atom in the central pyrrolidine ring of the spiro-fused system—namely, 2-selenoxodispiro[imidazolidine-4,3′-pyrrolidine-2′,3′′-indoline]-2′′, 5-diones (5a-h) and 2-senenoxodispiro[imidazolidine-4,3′-pyrrolidine-4′,3′′-indoline]-2′′,5-diones (6a-m)—were developed based on a 1,3-dipolar cycloaddition of azomethine ylides generated from isatin and sarcosine or formaldehyde and sarcosine to 5-arylidene or 5-indolidene-2-selenoxo-tetrahydro-4H-imidazole-4-ones. Selenium-containing dispiro indolinones generally exhibit cytotoxic activity near to the activity of the corresponding oxygen and sulfur-containing derivatives. Compounds 5b, 5c, and 5e demonstrated considerable in vitro cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) test (concentration of compounds that caused 50% death of cells (CC50) 7.6–8.7 μM) against the A549 cancer cell line with the VA13/A549 selectivity index 5.2– 6.9 and compound 6e—against the MCF7 cancer cell line (CC50 20.6 μM, HEK293T/A549 selectivity index 1.6); some compounds (5 and 6) increased the level of intracellular reactive oxygen species (ROS) in the experiment on A549 and PC3 cells using platinized carbon nanoelectrode. The tests for p53 activation for compounds 5 and 6 on the transcriptional reporter suggest that the investigated compounds can only have an indirect p53-dependent mechanism of action. For the compounds 5b, 6b, and 6l, the ROS generation may be one of the significant mechanisms of their cytotoxic action.

Silver-Catalyzed Acyl Nitrene Transfer Reactions Involving Dioxazolones: Direct Assembly of N-Acylureas

Dioxazolones and isocyanides are useful synthetic building blocks, and have attracted significant attention from researchers. However, the silver-catalyzed nitrene transfer reaction of dioxazolones has not been investigated to date. Herein, a silver-catalyzed acyl nitrene transfer reaction involving dioxazolones, isocyanides, and water was realized in the presence of Ag2O to afford a series of N-acylureas in moderate to good yields.

Isocyanide 2.0

The isocyanide functionality due to its dichotomy between carbenoid and triple bond characters, with a nucleophilic and electrophilic terminal carbon, exhibits unusual reactivity in organic chemistry exemplified for example in the Ugi reaction. Unfortunately, the over proportional use of only a few isocyanides hampers novel discoveries about the fascinating reactivity of this functional group. The synthesis of a broad range of isocyanides with multiple functional groups is lengthy, inefficient, and exposes the chemist to hazardous fumes. Here we present an innovative isocyanide synthesis overcoming these problems by avoiding the aqueous workup which we exemplify by parallel synthesis from a 0.2 mmol scale performed in 96-well microtiter plates up to a 0.5 mol multigram scale. The advantages of our methodology include an increased synthesis speed, very mild conditions giving access to hitherto unknown or highly reactive classes of isocyanides, rapid access to large numbers of functionalized isocyanides, increased yields, high purity, proven scalability over 5 orders of magnitude, increased safety and less reaction waste resulting in a highly reduced environmental footprint. For example, the hitherto believed to be unstable 2-isocyanopyrimidine, 2-acylphenylisocyanides and even o-isocyanobenzaldehyde could be accessed on a preparative scale and their chemistry was explored. Our new isocyanide synthesis will enable easy access to uncharted isocyanide space and will result in many discoveries about the unusual reactivity of this functional group. This journal is