3-Ethoxy-2,6-difluorophenol, JRD, 97% synthesis

Yield: 99%

Reaction Conditions:

with dihydrogen peroxide;acetic acid in tetrahydrofuran;water at 0 - 20;

Steps:

116
acid [1-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl-methyl)-1H-pyrazol-3-yl]-amide To a solution of 3-ethoxy-2,6-difluoro-phenylboronic acid (5.0 g, 0.025 mol) in tetrahydrofuran (80 mL) was added glacial acetic acid (30 mL). The resulting mixture was cooled to 0° C. before hydrogen peroxide (50% aqueous solution, 4 mL) was added. The resulting mixture was allowed to come to room temperature and stirred for 65 h. The mixture was evaporated and the residue was dissolved in ethyl acetate, washed with hydrochloric acid (0.5N), water and brine. The organic phase was dried, filtered and evaporated which afforded 3-ethoxy-2,6-difluoro-phenol (4.25 g, 99%) as a brown oil.

References:

Berthel, Steven Joseph;Brinkman, John A.;Hayden, Stuart;Haynes, Nancy-Ellen;Kester, Robert Francis;McDermott, Lee Apostle;Qian, Yimin;Sarabu, Ramakanth;Scott, Nathan Robert;Tilley, Jefferson Wright US2009/264445, 2009, A1 Location in patent:Page/Page column 94