Ethyl Acetate → 7-Methyloxymethyloxy-4-trifluoromethylcoumarin

Participants

Reaction Steps

7-Methyloxymethyloxy-4-trifluorocoumarin (MOMFC) was prepared as follows: A mixture of 7-hydroxy-4-trifluoromethylcoumarin (230 mg, 1 mmol) and K2CO3 (248 mg, 1.5 mmol), in DMF (15 mL) was vigorously stirred at 0–5° C. for 25 min. Bromomethyl methyl ether (0.97 mL, 10.0 mmol), was then added quickly to the reaction. The bright yellow mixture was stirred at 0–5° C. for 45 min during which time the reaction turned to a colorless solution. The reaction was allowed to continue to stir at 0–5° C. while monitoring by TLC (Rf=0.54, 1:1 EtOAc/:Hexane and Rf=0.24, CHCl3) and stopped at the time when product decomposition was detected. The reaction was then brought up in Et2O (35 mL), extracted with 30 mL of a saturated NaHCO3 solution. The aqueous layer was extracted two more times with Et2O (30 mL), the ether fractions were then combined, dried with anhydrous NaSO4, filtered and evaporated under reduced pressure. Chromatography of the crude product on silica gel (gradient 0–5% MeOH in CHCl3) gave 11 mg of the purified 7-methyloxymethyloxy-4-trifluoromethylcoumarin (MOMFC) as a white solid. 1H NMR (500 MHz, CDCl3): δ 03.49 (s, 3H), 5.26 (s, 2H), 6.64 (s, 1H), 7.08–7.02 (m, 2H), 7.64 (d, 1H).

Provenance & Evidence