Hydrochloric Acid → 3-Fluoro-4-methylanisole

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-methoxy-2-methyl aniline (5.0 g; 36 mmol), HCl (7.6 mL of a 12 M solution; 91 mmol) and H2O (11 mL) was heated at 60° C. for 15 min until complete dissolution had occurred. The reaction was cooled to 0° C. and an aqueous solution of NaNO2 (2.5 g; 36 mmol) was added dropwise (internal temperature<7° C.). The reaction was stirred at 0° C. for 30 min and a 0° C. solution of HBF4 (5.3 mL of a 48% solution; 40 mmol) was added cautiously. The reaction was stirred at 0° C. for 20 min, and the resultant brown solid was filtered, washed with ice water (3×10 mL) and H2O (2×10 mL). The solid was dried under high vacuum for 20 h, then heated (heat gun) until evolution of BF3 (white fumes) had ceased. The resulting brown oil was partitioned between EtOAc and H2O. The organic phase was dried (Na2SO4), concentrated in vacuo and distilled by Kugelrohr to give 3-fluoro-4-methyl anisole (1.6 g; 31%) as a colorless oil.

Provenance & Evidence