2-Amino-3-bromo-5-fluoropyridine

2-Amino-3-bromo-5-fluoropyridine Property

Melting point:

61-63°C

Boiling point:

63-65℃

Density 

1.813±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

pka

1.86±0.49(Predicted)

form 

powder to crystal

color 

White to Almost white

CAS DataBase Reference

869557-43-7(CAS DataBase Reference)

Safety

Hazard Codes 

Xi,Xn

Risk Statements 

22-37/38-41

Safety Statements 

26-39

WGK Germany 

3

HS Code 

29333990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H318Causes serious eye damage

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.

2-Amino-3-bromo-5-fluoropyridine Chemical Properties,Usage,Production

Uses

2-Amino-3-bromo-5-fluoropyridine is a reactant used in the synthesis of cyano heteroaryl bromides.

Synthesis

The general procedure for the synthesis of 2-amino-3-bromo-5-fluoropyridine from 2-amino-5-fluoropyridine is as follows: Method C: Bromination reaction using sulfuric acid (H2SO4). This was done as follows: a solution of 93% sulfuric acid (12.5 kg, 119 mol) in water (26 L) was added to a 50 L reactor, followed by 2-amino-5-fluoropyridine (6.5 kg, 58 mol). The reaction temperature was adjusted to 30 °C and then bromine (10 kg, 63 mol) was added in 10 portions over 3 hours. The reaction mixture was stirred at 45 °C for 18 hours, followed by continued stirring at 50 °C for 5 hours. Upon completion of the reaction, the mixture was cooled to 15 °C and transferred to a 400 L reactor for post-processing. The products of the four reactions (4 x 6.5 kg) were combined and the reaction was quenched with a mixture of 50% sodium hydroxide (110 kg, 1375 mol) and sodium thiosulfate (1.8 kg, 11.4 mol) in water (100 L) at 50 °C, the quenching process lasted for 1-3 hours. The temperature was adjusted to 32 °C, the slurry was filtered and washed with water (80 L) to give a water-wet crude product (62 kg). The same operation was carried out for the second round of three reactions (3 x 6.5 kg of feedstock) to give a water-wet crude product (41 kg). The crude product (103 kg) was dissolved (partially insoluble) in toluene (280 kg) at 25-30 °C. After addition of brine (20 kg), phase separation could not be achieved due to the presence of solids. The mixture was filtered through a diatomaceous earth pad, washed with toluene and layered. The organic phase was concentrated to 347 L to remove residual water by azeotropy and used in the subsequent preparation of compound 3a. The product concentration was determined by aliquoting to be 181 g/L in a yield of 62.8 kg. An additional 600 g of product was obtained by extraction of the water/brine layer by ethyl acetate (10 L) and separated, which was treated by filtration through a pad of magnesium salts, evaporation, and hexane grinding. The overall yield was 82%.

References

[1] Patent: WO2015/73481, 2015, A1. Location in patent: Paragraph 0259-0260
[2] Patent: WO2016/183116, 2016, A1. Location in patent: Paragraph 0251; 0252; 0253
[3] Patent: WO2017/97234, 2017, A1. Location in patent: Paragraph 00405
[4] Patent: WO2011/143366, 2011, A1. Location in patent: Page/Page column 75
[5] Patent: WO2011/143365, 2011, A1. Location in patent: Page/Page column 154