| Identification | More | [Name]
Ethyl 2-(ethoxymethylene)acetoacetate | [CAS]
3788-94-1 | [Synonyms]
2-(ETHOXYMETHYLENE)-3-OXO-BUTANOIC ACID,ETHYL ESTER
ethyl 2-(ethoxymethylene)acetoacetate
Ethyl-(ethoxymethylene)acetoacetate
ETHYL A-(ETHOXYMETHYLENE)ACETOACETATE
2-(ETHOXYMETHYLENE)-3-OXO-BUTANOIC ACID,ETHYL ESTER 98+%
2-Acetyl-3-ethoxyacrylic acid ethyl ester | [EINECS(EC#)]
223-259-3 | [Molecular Formula]
C9H14O4 | [MDL Number]
MFCD06797311 | [Molecular Weight]
186.21 | [MOL File]
3788-94-1.mol |
| Chemical Properties | Back Directory | [Boiling point ]
266°C(lit.) | [density ]
1.049±0.06 g/cm3(Predicted) | [refractive index ]
1.4730 to 1.4770 | [storage temp. ]
Keep in dark place,Sealed in dry,Room Temperature | [form ]
powder to lump to clear liquid | [color ]
Light yellow to Yellow to Orange | [InChI]
InChI=1S/C9H14O4/c1-4-12-6-8(7(3)10)9(11)13-5-2/h6H,4-5H2,1-3H3 | [InChIKey]
FNASCUBBFNCFQO-UHFFFAOYSA-N | [SMILES]
C(OCC)(=O)C(=COCC)C(=O)C | [CAS DataBase Reference]
3788-94-1(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Uses]
Ethyl 2-(ethoxymethylene)acetoacetate is an active metabolite of leflunomide, a pyrimidine synthesis inhibitor with anti-inflammatory and immunomodulatory properties that reduces the number of activated central nervous system lymphocytes. | [Application]
Ethyl 2-(ethoxymethylene)acetoacetate is a mono-, di-, and trifunctional three-carbon electrophile in carbonyl reactions and cyclization reactions; a β-ketoester equivalent. | [Preparation]
Ethyl 2-(ethoxymethylene)acetoacetate is obtained by heating Ethyl Acetoacetate with Triethyl Orthoformate in Acetic Anhydride. | [Synthesis]
Step a) Synthesis of the intermediate 2-(ethoxymethylene)-3-oxobutanoic acid ethyl ester: A mixed solution of ethyl acetoacetate (20 g, 154 mmol), triethyl orthoformate (51.1 mL, 307 mmol) and acetic anhydride (43.5 mL, 461 mmol) was heated and reacted for 5 hrs at 130 °C. After completion of the reaction, the mixture was cooled to room temperature. Subsequently, excess triethyl orthoformate and acetic anhydride were removed by concentration under reduced pressure. The residual acetic anhydride and triethyl orthoformate were further removed by distillation under reduced pressure (30 mbar, 30-70°C). Finally, the target product ethyl 2-(ethoxymethylene)-3-oxobutanoate was purified by distillation (6 mbar, 80 °C to 128 °C) as a viscous yellow oil (22.8 g, 80% yield). The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3): δ 7.59-7.69 (m, 1H), 4.17-4.34 (m, 4H), 2.29-2.44 (m, 3H), 1.25-1.44 (m, 6H). | [storage]
May be kept for a few weeks at 0 °C in the dark with addition of hydroquinone. The enol ether hydrolyses slowly in contact with water. Use in a fume hood. | [References]
[1] Journal of Heterocyclic Chemistry, 2018, vol. 55, # 4, p. 946 - 950
[2] Mendeleev Communications, 2016, vol. 26, # 1, p. 54 - 56
[3] Patent: WO2011/83316, 2011, A1. Location in patent: Page/Page column 52-53
[4] Letters in Drug Design and Discovery, 2016, vol. 13, # 9, p. 912 - 920
[5] Journal of Medicinal Chemistry, 2012, vol. 55, # 7, p. 3563 - 3567 |
|
|