4-BROMO-2-(2-HYDROXYETHYL)PHENOL synthesis

Yield:198277-06-4 126.0 g (94%)

Reaction Conditions:

with hydrogenchloride;sodium hydroxide in tetrahydrofuran;water;

Steps:

10.A 6-{2-[2-(3-Chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-chroman-2,2-dicarboxylic acid diethyl ester

A. 4-Bromo-2-(2-hydroxy-ethyl)-phenol (10a): A solution of borane-methyl sulfide complex (371 mL, 0.742 mol, 2M in THF) was added dropwise over about 1.5 hours to a solution of 143.0 g (0.619 mol) of 5-bromo-2-hydroxyphenylacetic acid in 1400 mL of dry THF, keeping the reaction temperature below about 30° C. The reaction mixture was stirred overnight at room temperature. Then, it was cooled to about 0° C., and 5M NaOH (706 mL) was added slowly with stirring, keeping the temperature below about 10° C. The reaction mixture was then was stirred in an ice bath for about 0.5 hour and at room temperature for about 2 hours. The THF was evaporated and the oily residue was diluted with 300 mL of water. A cold solution of 3M HCl was added slowly to pH 7, and the mixture was extracted three times with 300 mL of ethyl acetate. The combined organic layers were washed with water, brine, dried (Na₂ SO₄) and concentrated to a light yellow oil. This was triturated in 300 mL hexanes and filtered to give 126.0 g (94%) of 10a as a tan solid, mp 63°-65° C. ¹ H NMR (CDCl₃): d=9.50 (s, 1 H); 7.16 (s, 1 H); 7.06 (d, 1H); 6.66 (d, 1 H); 4.63 (br, 1 H); 3.55 (t, 2 H); 2.62 (t, 2 H). MS (El): m/z=218 (M+1).

References:

US5843972,1998,A