3-Amino-2-naphthoic acid → 3-Fluoronaphthalene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-amino-2-naphthoic acid (3.74 g, 20 mmol) and 48% fluoroboric acid (2.07 g, 30 mmol) in 10 mL of H2O cooled to 0° C. is added dropwise a solution of NaNO2 (2.07 g, 30 mmol) in 15 mL of H2O. The mixture is stirred at 0° C. for 1 hour. The mixture is filtered and the solids washed with cold H2O, then MeOH, then Et2O. The remaining solid is dried in vacuo at 40° C. for 2 days. The solid is suspended in xylene and heated to reflux for 8 hours and then cooled to room temperature. To the mixture is added hexane. The solid is filtered and washed with CH2Cl2, and dried to give 3-fluoro-2-naphthoic acid as a brown solid. A mixture of this solid and 80 mL of 1,4-dioxane is added to DPPA (4.5 mL, 20.9 mmol). Then 3.88 mL (27.9 mmol) of Et3N is added and the mixture is stirred for 2 hours at room temperature-under an atmosphere of nitrogen; Ethanol (8.1 mL, 139 mmol) is added, the mixture is heated to reflux for 2 hours, concentrated in vacuo and the residue diluted with 200 mL of EtOAc. The solution is washed with 5% aqueous Na2CO3 (50 mL), brine (50 mL), dried over MgSO4 and evaporated to dryness to give a solid that is purified by flash chromatography on silica gel (100% CH2Cl2) to give N-(3-fluoro-2-naphthyl)carbamic acid ethyl ester.

Provenance & Evidence