4-FLUORO-3-NITROBENZYL ALCOHOL 96

4-FLUORO-3-NITROBENZYL ALCOHOL 96 Property

Melting point:

39-44 °C (lit.)

Boiling point:

333.7±27.0 °C(Predicted)

Density 

1.434

Flash point:

230 °F

storage temp. 

Sealed in dry,Room Temperature

pka

13.37±0.10(Predicted)

Appearance

Light yellow to yellow Solid

Safety

Hazard Codes 

Xi

Risk Statements 

36

Safety Statements 

26

WGK Germany 

3

HS Code 

2906290090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H319Causes serious eye irritation

Precautionary statements

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

4-FLUORO-3-NITROBENZYL ALCOHOL 96 Chemical Properties,Usage,Production

Uses

4-Fluoro-3-nitrobenzyl Alcohol is used as a reagent in the preparation of EW-7197 (E950000) which is a highly potent orally bioavailable inhibitor of TGF-β type I receptor kinase that is used in cancer treatment as an immunotherapeutic or antifibrotic agent.

Uses

4-Fluoro-3-nitrobenzyl alcohol may be used in the synthesis of 4-fluoro-3-nitrobenzyl chloride.

General Description

4-Fluoro-3-nitrobenzyl alcohol can be prepared from the reaction between borane (in THF) and 4-fluoro-3-nitrobenzoic acid (in THF) at 0°C.

Synthesis

The general procedure for the synthesis of 3-nitro-4-fluorobenzyl alcohol from 4-fluoro-3-nitrobenzoic acid was as follows: sodium borohydride (2.70 g, 64.83 mmol) was dissolved in 100 mL of tetrahydrofuran and cooled to 0 °C. 4-Fluoro-3-nitrobenzoic acid (12.0 g, 64.83 mmol) was added in batches at 0 °C and the addition process lasted for 1 hour. Subsequently, boron trifluoride diethyl ether solution (6.55 mL, 71.31 mmol) was added dropwise at 0 °C. The reaction mixture was slowly warmed to room temperature and stirring was continued for 3 hours. Upon completion of the reaction, 500 mL of ethyl acetate and 300 mL of water were added to the mixture, which was layered and the organic phase was collected. The organic phase was washed with 500 mL of saturated sodium chloride solution and then dried with anhydrous sodium sulfate. The dried organic phase was filtered and the filtrate was concentrated under reduced pressure to give 3-nitro-4-fluorobenzyl alcohol (11.0 g, light yellow solid) in 99.1% yield.

References

[1] Patent: CN107400092, 2017, A. Location in patent: Paragraph 0293; 0295-0298
[2] Patent: CN108264511, 2018, A. Location in patent: Paragraph 0280; 0283-0286
[3] Patent: WO2012/171488, 2012, A1. Location in patent: Page/Page column 22-23
[4] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 23, p. 5546 - 5550
[5] Patent: WO2017/89453, 2017, A1. Location in patent: Page/Page column 54