2-Fluoro-4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)benzonitrile Chemical Properties

Boiling point:

346.6±32.0 °C(Predicted)

Density 

1.12±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

form 

Solid

Appearance

White to off-white Solid

InChI

InChI=1S/C13H15BFNO2/c1-12(2)13(3,4)18-14(17-12)10-6-5-9(8-16)11(15)7-10/h5-7H,1-4H3

InChIKey

DMJGKVYFBOCENL-UHFFFAOYSA-N

SMILES

C(#N)C1=CC=C(B2OC(C)(C)C(C)(C)O2)C=C1F

CAS DataBase Reference

870238-67-8

Safety Information

HS Code 

2931900090

2-Fluoro-4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)benzonitrile Usage And Synthesis

Uses

2-Fluoro-4-(4,4,5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile is used as an intermediate for Capmatinib. Capmatinib is an anti-cancer drug used to treat metastatic non-small cell lung cancer.

Synthesis

4-Bromo-2-fluorobenzonitrile (4.0 g, 20 mmol), pinacol ester of bisboronic acid (3.8 g, 30 mmol), and potassium acetate (6.1 g, 60 mmol) were suspended in dimethyl sulfoxide (DMSO, 50 mL) under nitrogen protection. Subsequently, [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride (Pd(dppf)Cl2, 1.5 g, 0.2 mmol) was added. The reaction mixture was stirred at 80 °C for 4 hours. After completion of the reaction, the mixture was diluted with water (100 mL) and extracted with ethyl acetate (100 mL × 3). The organic layers were combined and washed sequentially with water (50 mL × 3) and saturated saline (50 mL), then dried with anhydrous sodium sulfate. After drying, the filtrate was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent ratio: petroleum ether/ethyl acetate = 50:1 to 10:1) to afford the target product 4-cyano-3-fluorophenylboronic acid pinacol ester (56-a, 3.6 g, 73% yield). The product was characterized by 1H-NMR (400 MHz, CD3OD): δ 7.62 (m, 3H), 1.35 (s, 12H) ppm.

References

[1] Patent: US2015/336982, 2015, A1. Location in patent: Paragraph 0365; 0366; 0367
[2] Patent: WO2009/32861, 2009, A1. Location in patent: Page/Page column 45; 46
[3] Patent: WO2010/59658, 2010, A1. Location in patent: Page/Page column 149

2-Fluoro-4-(4,4,5,5-tetraMethyl-1,3,2-dioxaborolan-2-yl)benzonitrile(870238-67-8)Related Product Information

• Boric acid