Water → (4-Benzyloxy-6-fluoro-3-methyl-naphthalen-2-yl)-methanol

Participants

Reaction Conditions

Reaction Steps

A round-bottom flask was charged with lithium aluminum hydride (3.5 g, 88 mmol), and the flask was placed in an brine/ice bath. Tetrahydrofuran (100 mL) was added slowly. The resulting solution was maintained at −4° C. with stirring. A solution of 4-benzyloxy-6-fluoro-3-methyl-naphthalene-2-carboxylic acid methyl ester (14.27 g, 44.00 mmol) in tetrahydrofuran (30 mL) was slowly added to the cold lithium aluminum hydride suspension drop-wise via an addition funnel. The rate of drop-wise addition was monitored so that the reaction temperature did not exceed 6° C. After the drop-wise addition was complete, the reaction was warmed to room temperature. The reaction mixture was stirred at room temperature for 1 hour. After this time, the reaction mixture was cooled to 4° C. in an ice bath. Water (3.5 mL) was added slowly, keeping the reaction temperature below 4° C. A 15% aqueous NaOH solution (3.5 mL) was next added, followed by an additional portion of water (10.5 mL). The precipitated solids were filtered, and then rinsed with ethyl acetate. The combined filtrates were concentrated to obtain 13.09 g (quantitative yield) of (4-benzyloxy-6-fluoro-3-methyl-naphthalen-2-yl)-methanol as a white solid. This product was used in the next step without additional purification. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.00 (dd, J=8.9, 5.9 Hz, 1 H), 7.77 (s, 1 H), 7.54-7.63 (m, 3 H), 7.31-7.51 (m, 4 H), 5.26-5.35 (m, 1 H), 4.94 (s, 2 H), 4.64 (d, J=5.1 Hz, 2 H), 2.34 (s, 3 H).

Provenance & Evidence