3,4-dihydro-2H-pyran → 2-(3-fluorophenoxy)tetrahydro-2H-pyran

Participants

Reaction Steps

To 75 g (669 mmol) of 3-fluorophenol at -35 ° C. was added 79 g (928 mmol) of 3,4-dihydro-2H-pyran. The ice bath was removed and added 1.0 mL of concentrated HCl. The temperature was allowed to warm to room temperature and the reaction progress was monitored by HPLC. 500 ml of diethyl ether and 500 mL of 1 M NaHCO3 were added to the reaction. The organic layers were washed with NaHCO3 (2×) and brine. The organic layers were dried over Na2SO4, filtered, and concd to afford a yellow oil which was purified by silica gel chromatography with EtOAc/hexane (1:9). Concentration of the desired fractions afforded 102.1 g (78%) of a white solid: 1H NMR (CDCl3/400 MHz) 1.56-2.03 (m, 6H), 3.58-3.63 (m, 1H), 3.85-3.91 (m, 1H), 5.39 (t, 1H, J=3.2 Hz), 6.65-6.70 (m, 1H), 6.78-6.84 (m, 2H), 7.21 (dd, 1H, J=8.2, 15.0 Hz); HRMS (EI+) m/z calcd for (C11H13FO2) 196.0900, found 196.0890.

Provenance & Evidence