2,6-Lutidine → 3-Fluoropropyl trifluoromethanesulfonate

Participants

Reaction Steps

To a cold (−25° C.), stirred solution of 2,6-lutidine (4.60 mL, 39.5 mmol) in DCM (30 mL) was added triflic anhydride (6.00 mL, 35.5 mmol) over 3 min. Then 3-fluoropropane-1-ol (1.61 g, 20.6 mmol) was added. The reaction mixture was warmed to room temperature for 2.5 h. The reaction mixture was then concentrated to half its volume and purified by flash chromatography (Teledyne ISCO CombiFlash, isocratic DCM, REDISEP® SiO2 120 g, detecting at 254 nM, and monitoring at 220 nM). Concentration of the appropriate fractions provided Intermediate S-3A (2.92 g, 67.4%). 1H NMR (400 MHz, chloroform-d) δ ppm 4.69 (2 H, t, J=6.16 Hz), 4.65 (1 H, t, J=5.50 Hz), 4.54 (1 H, t, J=5.61 Hz), 2.25 (1 H, dt, J=11.39, 5.86 Hz), 2.19 (1 H, dt, J=11.44, 5.94 Hz)

Provenance & Evidence