Ethyl 3-(4-fluorophenyl)-3-oxopropanoate

Ethyl 3-(4-fluorophenyl)-3-oxopropanoate Property

Melting point:

117-120℃

Boiling point:

117-120 °C(lit.)

Density 

1.174 g/mL at 25 °C(lit.)

refractive index 

n20/D 1.5040(lit.)

Flash point:

>230 °F

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

form 

clear liquid

pka

9.82±0.25(Predicted)

Specific Gravity

1.19

color 

Colorless to Almost colorless

InChI

InChI=1S/C11H11FO3/c1-2-15-11(14)7-10(13)8-3-5-9(12)6-4-8/h3-6H,2,7H2,1H3

InChIKey

SJUXLKYJKQBZLM-UHFFFAOYSA-N

SMILES

C1(=CC=C(F)C=C1)C(=O)CC(=O)OCC

CAS DataBase Reference

1999-00-4(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Safety Statements 

24/25

WGK Germany 

3

Hazard Note 

Irritant

HS Code 

29183000

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P312Call a POISON CENTER or doctor/physician if you feel unwell.

P321Specific treatment (see … on this label).

Ethyl 3-(4-fluorophenyl)-3-oxopropanoate Chemical Properties,Usage,Production

Chemical Properties

Colorless liquid

Uses

Reactant used as a precursor in:

• Condensation reactions with diamines via C-C bond cleavage for synthesis of benzimidazoles and perimidines for possible use as antimalarial treatments
• Base-promoted domino Michael addition / cyclization / elimination reactions for synthesis of hydroxybenzophenones
• Oxidative cross-coupling with indoles via dioxygen activation
• Cyclization of keto esters for synthesis of pyrones
• Lewis base catalyzed hydrosilylation for synthesis of α-acetoxy β-amino acid derivatives
• Conia-ene reactions for synthesis of methylenecyclopentane derivatives

General Description

Ethyl (4-fluorobenzoyl)acetate on condensation with benzofurazan oxide yields 2-(carboethoxy)-3-(4′-fluoro)phenylquinoxaline1,4-dioxide.

Synthesis

(Step 1) Diethyl carbonate (47.4 mL, 391 mmol) and sodium hydride (55 wt% paraffin oil dispersion, 23.7 g, 543 mmol) were sequentially added to a suspension of tetrahydrofuran (THF) at 60 °C, followed by slow addition of 4'-fluoroacetophenone (26.4 mL, 271 mmol). The reaction mixture was heated to reflux for 1 h. After cooling to room temperature, it was slowly poured into a mixture of acetic acid (33.6 mL, 586 mmol) and ice water (1 L). The reaction mixture was extracted with ether (2×500 mL), and the organic layer was washed with saturated aqueous sodium bicarbonate and saturated brine sequentially, dried over anhydrous sodium sulfate, and then the solvent was concentrated under reduced pressure to afford ethyl 3-(4-fluorophenyl)-3-oxopropanoate as a yellow oil (45.7 g, 100% yield, ketone formula: enol formula = 5:1). The product was characterized by 1H-NMR (400 MHz, CDCl3): keto formula: δ 1.26 (3H, t, J=7.2 Hz), 3.97 (3H, s), 4.22 (2H, q, J=7.2 Hz), 7.13-7.19 (2H, m), 7.96-8.01 (2H, m); enol formula: δ 1.34 (0.6H, t, J =7.2 Hz), 4.27 (0.4H, q, J=7.2 Hz), 5.61 (0.2H, s), 7.08-7.12 (0.4H, m), 7.76-7.80 (0.4H, m), 12.62 (0.2H, s).

References

[1] Molecules, 2004, vol. 9, # 3, p. 135 - 157
[2] Patent: EP2738170, 2014, A1. Location in patent: Paragraph 0465
[3] Tetrahedron Letters, 2014, vol. 55, # 14, p. 2212 - 2216
[4] Patent: US2014/213571, 2014, A1. Location in patent: Paragraph 0780
[5] Patent: EP1362846, 2003, A1. Location in patent: Page/Page column 41