5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Chemical Properties

Boiling point:

342.9±32.0 °C(Predicted)

Density 

1.19±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

Chloroform (Slightly), Methanol (Slightly)

pka

9.12±0.40(Predicted)

form 

Solid

color 

White to Off-White

5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol Usage And Synthesis

Uses

4-Chloro-2-hydroxyphenylboronic acid pinacol ester is a building block which has seen use in the preparation of 5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-ylacetic acid derivs. for treatment of HIV infection, and in the preparation of disubstituted pyridazine analogs useful in the treatment of SMN deficiency related diseases.

Synthesis

2-Bromo-5-chlorophenol (2.0 kg, 9.65 mol), pinacol ester of bisboronic acid (B2Pin2, 2.7 kg, 10.6 mol), potassium acetate (AcOK, 1.9 kg, 19.3 mol) and 1,4-dioxane (15 L) were added to a 30 L reactor. The mixture was stirred and displaced three times with nitrogen. Under nitrogen protection, dichloro-[1,1'-bis(diphenylphosphino)ferrocene]palladium(II) (PdCl2(dppf)-CH2Cl2, 100 g, 0.12 mol) was added, and the mixture was subsequently heated to 75 °C (if the reaction is exothermic and violent, the oil bath may be temporarily removed). The reaction system was warmed to 90 °C and kept for 16 h. HPLC monitoring showed complete reaction. After cooling to 35 °C, the reaction mixture was filtered through a diatomaceous earth pad and the resulting filtrate was a solution of 5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1.22 kg, 4.8 mol), which was used directly in the subsequent reaction. Mass spectrum (MS) m/z: 253.1 [M-H]? ; 1H NMR (CDCl3, 400 MHz) δ: 9.2 (br, 1H), 7.25 (d, J = 8 Hz, 1H), 6.64 (d, J = 1.6 Hz, 1H), 6.62 (dd, J = 8 Hz, J = 1.6 Hz, 1H), 1.05 (s, 12H).

References

[1] Patent: WO2014/28459, 2014, A1. Location in patent: Page/Page column 184

5-chloro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol(1377503-12-2)Related Product Information

• 2-Chloropyridine-4-boronic acid pinacol ester