1-(5-BROMO-2-FLUOROPHENYL)ETHANONE Chemical Properties

Melting point:

42 °C

Boiling point:

251℃

Density 

1.535

Flash point:

106℃

storage temp. 

Sealed in dry,Room Temperature

form 

Solid

color 

White to Orange to Green

Water Solubility 

Slightly soluble in water.

InChI

InChI=1S/C8H6BrFO/c1-5(11)7-4-6(9)2-3-8(7)10/h2-4H,1H3

InChIKey

XNRQIHIOKXQSPG-UHFFFAOYSA-N

SMILES

C(=O)(C1=CC(Br)=CC=C1F)C

Safety Information

HazardClass 

IRRITANT

HS Code 

2914390090

1-(5-BROMO-2-FLUOROPHENYL)ETHANONE Usage And Synthesis

Uses

5'-Bromo-2'-fluoroacetophenone is an intermediate used in pharmaceuticals.

Preparation

Synthesis of 1-(5-Bromo-2-fluorophenyl)ethanone: In a dry flask, a solution of 5-bromo-2-fluoro-N-methoxy-N-methylbenzamide (3.73 g, 14.2 mmol) in tetrahydrofuran (24 mL) was treated dropwise with a solution of methyl magnesium chloride (3 M in THF, 5.69 mL, 17 mmol) at 12–16 °C. After complete addition, the reaction mixture was heated to reflux. After 20 min, the resulting white suspension was quenched with saturated ammonium chloride solution (25 mL) under ice cooling. The mixture was then diluted with ethyl acetate (50 mL), and the aqueous layer was separated and re-extracted with ethyl acetate (50 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified to afford 1-(5-bromo-2-fluorophenyl)ethanone as a pale yellow solid (2.6 g, 84% yield), with an Rf = 0.55 (silica gel, eluent: heptane/ethyl acetate = 4:1).

Synthesis

Synthesis of 1-(5-bromo-2-fluorophenyl)ethanone (15): To a stirred solution of 5-bromo-2-fluoro-N-methoxy-N-methylbenzamide (14) (106 g, 404 mmol) in anhydrous tetrahydrofuran (THF) (1.7 L) was slowly added, under nitrogen protection and at 0 °C, an ether solution of methylmagnesium bromide (3.0 M, 270 mL, 808 (3.0 M, 270 mL, 808 mmol). After addition, the reaction was continued to be stirred at 0 °C for 6.5 hours. After completion of the reaction, the reaction solution was slowly poured into 2N hydrochloric acid (1 L) and gradually warmed to room temperature. The reaction mixture was extracted with ethyl acetate (2 x 1 L). The organic phases were combined, washed sequentially with saturated aqueous sodium bicarbonate (500 mL) and brine (500 mL), dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to afford the target product 15 (85.2 g, 97% yield) as an orange oil. The product was confirmed by 1H NMR (300 MHz, CDCl3): δ 7.98 (dd, J = 6.4, 2.6 Hz, 1H), 7.61 (ddd, J = 8.7, 4.3, 2.6 Hz, 1H), 7.05 (dd, J = 10.4, 8.7 Hz, 1H), 2.64 (d, J = 4.9 Hz, 3H); ESI MS m/ z 217 [M + H]+.

References

[1] Patent: WO2011/44184, 2011, A1. Location in patent: Page/Page column 103-104