Trifluoromethanesulfonic acid → Methyl 4-amino-6-(1-fluoroethyl)-3-methoxypicolinate

Participants

Reaction Conditions

Reaction Steps

To a −10° C. (ice+NaCl) suspension of methyl 4-amino-6-(1-hydroxyethyl)-3-methoxypicolinate (0.3 g, 1.326 mmol) in Chloroform (6.63 ml) was added dropwise Triflic Acid (0.141 ml, 1.591 mmol) followed by Deoxo-Fluor® (0.257 ml, 1.392 mmol). The suspension was stirred at −10° C. (LC monitoring). After 2 h, the reaction mixture was poured into saturated NaHCO3 and extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered and concentrated. The residue was purified by flash column chromatography (ISCO, SiO2 24 g, hexane/EtOAc 100:0 to 0:100 gradient) to afford methyl 4-amino-6-(1-fluoroethyl)-3-methoxypicolinate (175 mg, 0.767 mmol, 57.8% yield) as a white solid. ESIMS m/z 227 ([M−H]−); 1H NMR (400 MHz, CDCl3) δ 6.91 (s, 1H), 5.59 (dq, J=47.6, 6.3 Hz, 1H), 4.53 (s, 2H), 3.97 (s, 3H), 3.87 (s, 3H), 1.62 (dd, J=24.6, 6.4 Hz, 3H); 19F NMR (376 MHz, CDCl3) δ −176.20.

Provenance & Evidence