5-broMo-3-fluorobenzene-1,2-diol Chemical Properties

Boiling point:

263.2±35.0 °C(Predicted)

Density 

1.940±0.06 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Room Temperature

pka

7.84±0.15(Predicted)

Appearance

White to off-white Solid

Safety Information

HS Code 

2908190090

5-broMo-3-fluorobenzene-1,2-diol Usage And Synthesis

Uses

5-Bromo-3-fluorobenzene-1,2-diol is used as a reagent in the synthesis of N-(hydroxy(pyrrolidinyl)propanyl)pyrrolidinecarboxamide derivatives as glucosylceramide synthase inhibitors.5-Bromo-3-fluorobenzene-1,2-diol is also used in the preparation of 5,5-disubstituted-2-iminopyrrolidine derivatives as thrombin receptor antagonists.

Synthesis

General procedure for the synthesis of 5-bromo-3-fluoro-2-hydroxybenzene-1,2-diol from 5-bromo-3-fluoro-2-hydroxybenzaldehyde: Water was added slowly and dropwise to a solution of 5-bromo-3-fluoro-2-hydroxybenzaldehyde (40 g, 183 mmol) in tetrahydrofuran (THF, 260 mL). Sodium hydroxide (NaOH) solution (0.05N, 720 mL, 37 mmol) was added at 0 °C, followed by 30% hydrogen peroxide (H2O2) solution (90 mL). The reaction mixture was stirred at room temperature for 2 hours, then a second portion of 30% hydrogen peroxide (90 mL) was added. After continued stirring for 4 hours, the mixture was cooled to 0°C and washed with cold water. The pH was adjusted to 10-11 by adding sodium hydroxide solution (2N, 112 mL) and stirring was continued for 0.5 h. The reaction was subsequently quenched with concentrated hydrochloric acid (HCl). The pH was adjusted to 2-3 with hydrochloric acid at 0 °C. The reaction mixture was extracted with dichloromethane (250 mL x 3), the organic phases were combined and washed with brine (300 mL x 2), dried over anhydrous sodium sulfate (Na2SO4), and concentrated to give 5-bromo-3-fluorobenzene-1,2-diol (37 g, 98% yield) as a yellow oil. lc-MS (m/z): 205 [ M-H]-.

References

[1] Patent: WO2015/42397, 2015, A1. Location in patent: Paragraph 000236
[2] Patent: EP1780192, 2007, A1. Location in patent: Page/Page column 11
[3] Patent: WO2017/176960, 2017, A1. Location in patent: Paragraph 00730
[4] Patent: WO2015/65937, 2015, A1. Location in patent: Paragraph 000213
[5] Patent: WO2016/145153, 2016, A1. Location in patent: Paragraph 000179