Hydrochloric Acid → 3-fluorothiophene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

2-Thiophene-carboxylic acid (1.7 g, 13.3 mmol) was dissolved in anhydrous THF (30 mL) and the solution was cooled to −78° C. under Ar, with stirring. n-Butyllithium (18.3 mL, 29.3 mmol) in hexanes was added to the above solution and the mixture was stirred for 30 min. A solution of N-fluorobenzenesulfonimide (5 g, 15.9 mmol) in THF (30 mL) was then added and the resulting solution was stirred at −78° C. for 4 h and allowed to warm to ambient temperature over a period of 6 h. The reaction was diluted with diethyl ether (100 mL), cooled to 0° C., and 1 N HCl (15 mL) was added to give a biphasic mixture. The aqueous layer was isolated and washed with diethyl ether (3×50 mL). The combined ethereal layers were dried over MgSO4, filtered, and concentrated in vacuo to yield an orange oil. The oil was subjected to column chromatography on silica gel using 1:1 hexanes/ethyl acetate as the eluent. (14) was obtained as a slightly brown solid (0.777 g) in 40% yield. TLC (1:1 ethyl acetate/hexanes) Rf 0.17; 1H NMR (CDCl3) δ 10.7 (s, 1H), 7.53 (dd, J=5.4, 3.6 Hz, 1H), 6.89 (d, J=5.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 166.2 (d, J=3.5 Hz), 161.5 (d, J=278 Hz), 132.0 (d, J=10 Hz), 118.9 (d, J=24.7 Hz), 113.6; 19FNMR (282 MHz, CDCl3, CFCl3) δ-65.2 (d, J=6 Hz); EI-MS m/e 145.9838 (M+ calcd 145.9838 for C5H3FO2S).

Provenance & Evidence