Methanesulfonic Acid → 6-Benzyl4-trifluoromethylchromen-2-one

Participants

Reaction Conditions

Reaction Steps

A stirred suspension of 4-benzylphenol (4.67 g, 25.4 mmol), CF3COCH2CO2Et (7.00 g, 38.0 mmol), & MeSO3H (8.5 mL, 130.9 mmol) was heated at 65° C. for 9 h. On cooling, the mixture was partitioned between Et2O (200 mL) and H2O (50 mL), then the aqueous phase was basicified with 2 M NaOH. The organic layer was separated and washed with H2O and brine, before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (4:1 PE-Et2O) furnished 6-benzyl-4-trifluoromethylchromen-2-one (3.42 g, 44%): δH (CDCl3)=4.10 (s, 2H), 6.85 (s, 1H), 7.20–7.40 (m, 5H), 7.45 (dd, 1H), 7.60 (d, 1H). This compound (2.00 g, 6.6 mmol) was dissolved in H2SO4 (20 mL), then the whole was stirred for 15 minutes. The mixture was carefully treated with crushed ice (80 g), then the resulting white precipitate was collected by filtration. The precipitate was air-dried, before being treated with hot THF (100 mL). After filtration, the filtrate was concentrated to yield 4-(2-oxo-4-trifluoromethyl-2H-chromen-6-ylmethyl)benzenesulfonic acid (2.20 g, 87%): δH ((CD3)2SO)=4.05 (s, 2H), 7.00 (s, 1H), 7.20 (d, 2H), 7.45 (d, 1H), 7.50–7.60 (m, 4H). This compound was reacted with (COCl)2, as described above in Preparation 2, to give a solid which was dissolved in EtOAc, before being filtered and concentrated to produce the title compound (2.30 g, 87%): Rf (2:1 PE-EtOAc)=0.60.

Provenance & Evidence