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

HRID 1828263Notes

Reaction equation

HRID 1828263 reaction equation
[CH2:1]([C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([C:19]([CH2:21][C:22](OCC)=[O:23])=O)([F:18])([F:17])[F:16].CS(O)(=O)=O>>[CH2:1]([C:8]1[CH:13]=[C:12]2[C:11](=[CH:10][CH:9]=1)[O:14][C:22](=[O:23])[CH:21]=[C:19]2[C:15]([F:18])([F:17])[F:16])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 6395Methanesulfonic AcidHCID 75634-BenzylphenolHCID 67793Ethyl 4,4,4-trifluoroacetoacetate

Product 1

HCID 219767876-Benzyl4-trifluoromethylchromen-2-oneYield 44.3%

Conditions

Temperature
65 °C

Procedure

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.

Workup

  1. temperatureOn cooling
  2. customthe mixture was partitioned between Et2O (200 mL) and H2O (50 mL)
  3. customThe organic layer was separated
  4. washwashed with H2O and brine
  5. dry with materialbefore being dried (MgSO4)
  6. filtrationFiltration, solvent evaporation, and column chromatography (4:1 PE-Et2O)

Sources & evidence

ORD record
ord-c393382f3b7444b68041f5acbecd5289
Source dataset
uspto-grants-2006_06
Patent number
US07057048B2

Reaction notes

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