Water → N-[3-(2-Hydroxyethyl)-4-methoxy-[1,1'-biphenyl]-2-yl]-2,2-dimethylpropanamide

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Reaction Conditions

Reaction Steps

A mechanically stirred solution of N-(4-methoxybiphenyl-2-yl)-2,2-dimethylpropionamide (17.91 g, 63.2 mmol) in anhydrous THF at -68° C. was treated dropwise with butyllithium (2.46 M in hexane, 72.0 mL, 177 mmol), stirred 1 h, allowed to warm to -5° C., stirred 1 h, cooled to -78° C., and treated with ethylene oxide (10.0 mL, 8.82 g, 200 mmol) in one portion. The suspension was allowed to warm to room temperature and stirred for 12 h. The suspension was treated with water (50 mL) and glacial acetic acid (2 mL), stirred 10 min, and concentrated in vacuo. The residue was treated with water (500 mL) and Et2O (300 mL), and the layers were separated. The aqueous layer was further extracted with diethyl ether (2×300 mL), the combined organic extracts were washed with saturated sodium bicarbonate (500 mL), brine (500 mL), dried (K2CO3), filtered, and concentrated in vacuo to give a solid. Recrystallization from Et2O/hexanes gave 10.85 g (52%, 2 crops) of the compound as white crystals: 1H NMR (300 MHz, CDCl3) δ 1.04 (s, 9H), 2.00 (br s, 1H), 2.89 (t, J=6 Hz, 2H), 3.85 (s, 3H), 3.91 (t, J=6 Hz, 2H), 6.88 (d, J=8 Hz, 1H), 7.18 (d, J=8 Hz, 1H), 7.26-7.36 (m, 5H), 7.50 (br s, 1H).

Provenance & Evidence