Diethyl acetamidomalonate Chemical Properties

Melting point:

95-98 °C (lit.)

Boiling point:

185 °C/20 mmHg (lit.)

Density 

1.2850 (rough estimate)

refractive index 

1.4640 (estimate)

Flash point:

185°C/20mm

storage temp. 

Sealed in dry,Room Temperature

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

11.93±0.59(Predicted)

form 

Crystalline Powder

color 

White to light yellow

Water Solubility 

Soluble in chloroform and methanol. Slightly soluble in water.

BRN 

783883

InChIKey

ISOLMABRZPQKOV-UHFFFAOYSA-N

CAS DataBase Reference

1068-90-2(CAS DataBase Reference)

NIST Chemistry Reference

Propanedioic acid, (acetylamino)-, diethyl ester(1068-90-2)

EPA Substance Registry System

Propanedioic acid, 2-(acetylamino)-, 1,3-diethyl ester (1068-90-2)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36-36/37/38

Safety Statements 

39-36-26-44

WGK Germany 

3

RTECS 

OO0360000

TSCA 

Yes

HazardClass 

IRRITANT

HS Code 

29241900

Hazardous Substances Data

1068-90-2(Hazardous Substances Data)

Toxicity

eye-rbt 500 mg/24H MLD 28ZPAK -,130,72

MSDS

• Language:English Provider:Acetamidomalonic acid diethyl ester
• Language:English Provider:SigmaAldrich
• Language:English Provider:ACROS
• Language:English Provider:ALFA

Diethyl acetamidomalonate Usage And Synthesis

Chemical Properties

white to light yellow crystalline powder

Uses

Diethyl 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.

Chemical Reactivity

Diethyl acetamidomalonate is flammable; upon heating it decomposes releasing toxic nitrogen oxide fumes.

Safety Profile

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

Synthesis

Diethyl 2-aminomalonate hydrochloride (1.69 g, 8.0 mmol) and triethylamine (3.4 mL, 24 mmol, 3.0 eq.) were dissolved in dichloromethane (120 mL) at 0 °C. Acetyl chloride (0.57 mL, 8.0 mmol, 1.0 eq.) was added slowly and dropwise with stirring and the reaction mixture was gradually warmed to room temperature and stirred overnight. After completion of the reaction, the mixture was diluted with dichloromethane (100 mL) and washed sequentially with 1 M hydrochloric acid (3 x 60 mL). The aqueous phase was then back-extracted with dichloromethane (2 x 60 mL), the organic layers were combined and dried over anhydrous magnesium sulfate. The solvent was removed by concentration under reduced pressure to give a pure white solid product. Yield: 1.68 g (96% yield). The product was characterized as follows: melting point 96 °C (literature value 97 °C); 1H NMR (300 MHz, CDCl3) δ [ppm]: 1.30 (t, J=7.1Hz, 6H, 7-CH3,9-CH3), 2.08 (s, 3H, 5-CH3), 4.27 (m, 4H, 6-CH2,8-CH2), 5.18 (d, J=7.1Hz, 1H), 5.18 (d, J=7.1Hz, 1H). 7.1 Hz, 1H, 2-CH), 6.67 (d, J=5.7 Hz, 1H, 2-NH); 13C NMR (75 MHz, CDCl3) δ [ppm]: 14.0 (q, C-7, C-9), 22.8 (q, C-5), 56.5 (d, C-2), 62.6 (t, C-6, C-8), 166.5 (s, C -1, C-3), 169.9 (s, C-4); high-resolution mass spectrometry (ESI+): 240.0842 calculated value for C9H15N5O+Na+, 240.0824 measured value.

Purification Methods

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

References

[1] Patent: WO2013/26765, 2013, A1. Location in patent: Page/Page column 15-16
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 5, p. 1011 - 1026

Diethyl acetamidomalonate(1068-90-2)Related Product Information

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