2-(2-bromo-6-nitrophenyl)ethanol synthesis

Yield: 72%

Reaction Conditions:

with potassium hydroxide in N,N-dimethyl acetamide at 20; for 0.75 h;

Steps:

2 2-(2-bromo-6-nitroyhenyl)ethan-1-ol
Potassium hydroxide (5.71 g, 101.8 mmol) was added to a stirring solution of 1-bromo-2- methyl-3-nitrobenzene (20 g, 93 mmol) and paraformaldehyde (2.78 g, 92.6 mmol) in N,N5 dimethylacetamide (200 mL) at 20 °C. The resulting mixture was stirred at roomtemperature for 45 minutes and then diluted with ethyl acetate (200 mL) and washed with water (3x) and saturated aqueous sodium chloride. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by flash silica chromatography, elution gradient 0 to 60% EtOAc in hexanes. Product fractions wereconcentrated under reduced pressure to afford 2-(2-bromo-6-nitrophenyl)ethan- 1 -ol (16 g,72%) as a yellow solid. ‘H NMR (300MHz, DMSO-d6, 27°C) 3.09 (2H, t), 3.51 -3.66(2H, td), 4.89 (1H, t), 7.41 (1H, t), 7.86 (1H, dd), 7.96 (1H, dd). m/z: ES+ [M-OH+H]+227.

References:

ASTRAZENECA AB;SCOTT, James, Stewart;BARLAAM, Bernard, Christophe;YANG, Bin;HANDE, Sudhir, Mahadeo WO2019/2442, 2019, A1 Location in patent:Page/Page column 52; 53