2,6-Lutidine → 3-Fluoropropyl trifluoromethanesulfonate

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-fluorpropane-1-ol (Oakwood, cat. 010306-25G, 1.61 g, 20.6 mmol) was added. The reaction mixture was warmed to room temperature for 2.5 h. The reaction mixture was 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-6A (2.92 g, 67.4%). 1H NMR (400 MHz, chloroform-d) δ ppm 4.69 (2H, t, J=6.16 Hz), 4.65 (1H, t, J=5.50 Hz), 4.54 (1H, t, J=5.61 Hz), 2.25 (1H, dt, J=11.39, 5.86 Hz), 2.19 (1H, dt, J=11.44, 5.94 Hz).

1. concentrationThe reaction mixture was concentrated to half its volume
2. custompurified by flash chromatography (Teledyne ISCO CombiFlash, isocratic DCM, REDISEP® SiO2 120 g, detecting at 254 nM, and monitoring at 220 nM)
3. customConcentration of the appropriate fractions provided Intermediate S-6A (2.92 g, 67.4%)

ORD record

ord-56872bc9033044b39f79db77d0a725d9

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09427442B2