1-(2-Amino-6-fluorophenyl)ethanone

1-(2-Amino-6-fluorophenyl)ethanone Property

Boiling point:

255.2±20.0 °C(Predicted)

Density 

1.201±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

pka

1.29±0.10(Predicted)

Appearance

Light yellow to yellow Solid

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

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

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

P310Immediately call a POISON CENTER or doctor/physician.

1-(2-Amino-6-fluorophenyl)ethanone Chemical Properties,Usage,Production

Synthesis

1. Methylmagnesium bromide (85.76 mL, 3.0 M ethyl ether solution) was added slowly and dropwise to a 20 mL THF solution of 2-amino-6-fluorobenzonitrile (5.0 g, 37 mmol) at -10°C. After the dropwise addition was completed, the reaction mixture was warmed to 70°C and stirred for 5 hours. Upon completion of the reaction, the reaction was quenched with 30 mL of 10% HCl solution and heated to reflux for 1 hour. Subsequently, the pH was adjusted to basic with NaHCO3 and extracted with EtOAc (30 mL x 3). The organic layers were combined, concentrated in vacuum and purified by silica gel column chromatography (eluent: PE/EtOAc = 100:1) to afford 1-(2-amino-6-fluorophenyl)ethanone (2.09 g, yield: 36.8%). 2. 1-(2-Amino-6-fluorophenyl)ethanone (2.0 g, 13.3 mmol) was dissolved in 35 mL of THF, DMAP (1.596 g, 16.6 mmol) and trichloroacetyl chloride (2.42 g, 13.3 mmol) were added, and the mixture was stirred at 0 °C. Subsequently, the reaction mixture was warmed to room temperature and stirred for 7 hours. After completion of the reaction, it was diluted with 50 mL of ice water and extracted with EtOAc (15 mL x 3). The organic layers were combined, concentrated in vacuum and purified by silica gel column chromatography (eluent: PE/EtOAc = 60:1) to afford Intermediate 4b (3.0 g, yield: 75.76%). Mass spectral data: m/z = 297 [M + H]+. 3. Intermediate 4b (1.4 g, 4.7 mmol) was dissolved in 10 mL of DMSO, ammonium acetate (1.3 g, 23 mmol) was added, and stirred at room temperature for 24 hours. After the reaction was completed, it was diluted with cold water, the precipitate was collected by filtration and dried under vacuum to give 5-fluoro-4-methyl-1H-quinazolin-2-one (0.8 g, yield: 95.6%). The product could be used in the next reaction without further purification. Mass spectral data: m/z = 179 [M + H]+. 4. 5-Fluoro-4-methyl-1H-quinazolin-2-one (300 mg, 1.68 mmol) was mixed with 3 mL of POCl3 and stirred at 80°C for 12 hours. After completion of the reaction, the mixture was poured into 20 mL of aqueous K2CO3 and extracted with EtOAc (5 mL x 3). The organic layers were combined, concentrated in vacuum and purified by silica gel column chromatography (eluent: PE/EtOAc = 50:1) to afford 2-chloro-5-fluoro-4-methyl-quinazoline (140 mg, yield: 42.5%) as a white solid. Mass spectral data: m/z = 197 [M + H]+.

References

[1] Patent: WO2013/50527, 2013, A1. Location in patent: Page/Page column 46; 47