(3-broMo-2-Methylphenyl)Methanol Chemical Properties

Melting point:

103-104 °C(Solv: benzene (71-43-2))

Boiling point:

286.4±25.0 °C(Predicted)

Density 

1.481±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

form 

crystalline needles

pka

14.29±0.10(Predicted)

color 

Faint beige to faint brown

Safety Information

HS Code 

2906290090

(3-broMo-2-Methylphenyl)Methanol Usage And Synthesis

Application

3-Bromo-2-methylbenzyl alcohol is an organic synthesis intermediate and a pharmaceutical intermediate that can be used in laboratory research and development processes as well as in chemical and pharmaceutical synthesis.

Description

3-Bromo-2-methylbenzyl alcohol is a pharmaceutical intermediate, which is obtained by esterification and reduction of 3-bromo-2-methylbenzoic acid. Literature reports that 3-bromo-2-methylbenzyl alcohol can be used to prepare fused ring compounds as PD-1/PD-L1 inhibitors, which have the advantages of high activity, high bioavailability, drug stability, and oral administration.

Synthesis

(1) Synthesis of (3-bromo-2-methylphenyl)methanol [99-1] (hereinafter referred to as compound [99-1]) 3-Bromo-2-methylbenzoic acid (1.08 g, 5.0 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL) and cooled in an ice bath to 0°C. To this solution, sodium borohydride (1.15 g, 30.4 mmol) was added batchwise under stirring. Subsequently, a tetrahydrofuran (16 mL) solution of iodine (3.81 g, 15.0 mmol) was added to the reaction mixture in two slow drops. After addition, the ice bath was removed and the reaction mixture was stirred at room temperature for 20 hours. Upon completion of the reaction, the reaction was quenched by the slow addition of 4N hydrochloric acid (20 mL) under the cooling of the ice bath. The reaction mixture was extracted with ethyl acetate (3 × 20 mL) and the organic phases were combined. The organic phase was washed sequentially with 2N aqueous sodium hydroxide (20 mL) and saturated saline (20 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting crude product was purified by silica gel column chromatography (eluent: petroleum ether/ethyl acetate = 4:1) to afford the title compound (3-bromo-2-methylphenyl)methanol (934 mg, 86% yield) as a white solid. 1H-NMR (400 MHz, CDCl3) δ: 7.52-7.50 (1H, m), 7.32 (1H, d, J = 7.6 Hz), 7.06 (1H, t, J = 7.8 Hz), 4.73 (2H, d, J = 5.9 Hz), 2.43 (3H, s), 1.58 (1H, t, J = 5.9 Hz).

References

[1] Journal of Medicinal Chemistry, 2017, vol. 60, # 13, p. 5857 - 5867
[2] Patent: WO2017/118762, 2017, A1. Location in patent: Page/Page column 39
[3] Patent: US2006/173183, 2006, A1. Location in patent: Page/Page column 119-120
[4] Patent: WO2006/128184, 2006, A2. Location in patent: Page/Page column 144-145
[5] Patent: US2008/21024, 2008, A1. Location in patent: Page/Page column 63

(3-broMo-2-Methylphenyl)Methanol(83647-43-2)Related Product Information

• 4-Hydroxybenzyl alcohol
• 3-Bromo-2-methylbenzoic acid
• 3-BROMO-2-METHYLBENZONITRILE
• 4-Bromo-3-methylbenzoic acid
• bis(2-ethylhexyl) tetrabromophthalate