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) & H2O (50 mL), then the aqueous phase was basicified with 2 M NaOH. The organic layer was separated & washed with H2O & brine, before being dried (MgSO4). Filtration, solvent evaporation, & column chromatography (4:1 PE-Et2O) furnished 6-benzyl4-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 min. 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 1, to give a solid which was dissolved in EtOAc, before being filtered & concentrated to produce the title compound (2.30 g, 87%): Rf (2:1 PE-EtOAc)=0.60.

Provenance & Evidence