Water → Ethyl 2-tert-butoxy-2-(4-fluoro-1-hydroxy-3-methylnaphthalen-2-yl)acetate

Participants

Reaction Conditions

Reaction Steps

A solution of ethyl 2-tert-butoxy-2-(1-hydroxy-3-methylnaphthalen-2-yl)acetate (1.50 g, 4.74 mmol) in CH3CN (37.5 mL) was cooled to 0° C. Selectfluor (1.70 g, 4.74 mmol) was added, and the reaction was allowed to warm to 23° C. After 2 h, the reaction was added slowly to a mixture of saturated Na2HPO4 (70 mL) and H2O (30 mL) at 23° C. More H2O (40 mL) was added, and the system was extracted with DCM (3×40 mL). The combined organic phases were treated with hexane (20 mL). The phase that separated was removed. The remaining organic phase was dried (Na2SO4), filtered, and concentrated. The filtrate was concentrated and dissolved in benzene. The solution was wet-loaded onto a 24 g “gold” ISCO silica gel column and purified by flash chromatography (ethyl acetate/hexanes) giving the desired product (1.26 g, 79%). 1H NMR (400 MHz, CDCl3) δ 8.83 (s, 1H), 8.23 (d, J=8.2 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.51 (dd, J=6.9, 6.9 Hz, 1H), 7.45 (dd, J=6.9, 6.9 Hz, 1H), 5.46 (s, 1H), 4.23-4.14 (m, 2H), 2.49 (d, JHF=3.2 Hz, 3H), 1.31 (s, 9H), 1.20 (t, J=7.1 Hz, 3H). 19F NMR (377 MHz, CDCl3) δ−137.3 (app. s).

Provenance & Evidence