Uses
3-(Bromomethyl)phenol is a reagent used in synthesis of furan-based heterocycles. Also used in the preparation of tetrahydroisoquinolinyl triazole carboxamide and triazole substituted benzamide analogues as σ2 receptors.
Synthesis
General procedure for the synthesis of m-hydroxybenzyl bromide from 3-hydroxybenzyl alcohol:
Synthesis of Intermediate 17: 3-(bromomethyl)phenol
A 50 mL round bottom flask was charged with 15 mL of dichloromethane and fitted with a magnetic stirrer. To the stirred solvent was added 3-hydroxymethylphenol (0.5 g, 4.03 mmol). After cooling the reaction mixture to 0°C, phosphorus tribromide (1.6 g, 0.56 mL, 6.04 mmol) was added dropwise. After the dropwise addition, the reaction mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction mixture was diluted with 25 mL of dichloromethane and the organic layer was washed with 20 mL of water. The organic layer was dried with anhydrous Na2SO4 and concentrated under reduced pressure to remove the solvent to give a brown solid product (0.65 g, yield: 86.3%).
Mass spectrum (ESI, 120 eV): m/z = 187.0 (M + H)+.
1H NMR (300MHz, CDCl3): δ 7.10-7.15 (t, 1H), 6.86-6.89 (d, 1H), 6.80 (d, 1H), 6.67-6.71 (m, 1H), 4.35-4.36 (d, 2H), 3.80-3.94 (broad peak, 1H).
References
[1] Chemische Berichte, 1989, vol. 122, p. 347 - 356
[2] Patent: WO2012/11125, 2012, A1. Location in patent: Page/Page column 70; 71-72
[3] Patent: WO2014/31936, 2014, A2. Location in patent: Paragraph 0327; 0328
[4] Patent: WO2014/31928, 2014, A2. Location in patent: Paragraph 0334
[5] Patent: WO2005/68421, 2005, A1. Location in patent: Page/Page column 39-40
