Dimethyl Sulfoxide → 3-[5-Methyl-3-(2-trifluoromethylbenzyloxy)phenoxy]propionaldehyde

Sulfur trioxide pyridine complex (1.3 g, 8.0 mmol) was added to a solution of 3-[5-methyl-3-(2-trifluoromethylbenzyloxy)phenoxy]propanol (680 mg, 2.0 mmol), as prepared in the preceding step, N,N-diisopropylethylamine (0.7 mL, 5.5 mmol) and anhydrous dimethyl sulfoxide (0.4 mL, 5.6 mmol) in anhydrous dichloromethane (20 mL). The reaction mixture was stirred at ambient temperature for 1 hour and then quenched with 10% aqueous citric acid (50 mL). The mixture was extracted into dichloromethane (3×50 mL), and the dichloromethane solution was washed with 10% aqueous citric acid (40 mL) and dried over Na2SO4. After removing the solvent in vacuo, the residue was purified by flash column chromatography (dichloromethane) to give the title compound as a white solid (575 mg, 85%). 1H-NMR (300 MHz, CDCl3) δ 9.85 (s, 1 H), 7.75 (d, J=7.8 Hz, 1 H), 7.69 (d, J=7.8 Hz, 1 H), 7.56 (t, J=7.6 Hz, 1 H), 7.41 (t, J=7.6 Hz, 1 H), 6.42 (s, 1H), 6.37 (s, 1 H), 6.35 (s, 1 H), 5.23 (s, 2 H), 4.27 (t, J=6.1 Hz, 2 H), 2.87 (t, J=6.1 Hz, 2 H), 2.29 (s, 3 H).

1. customquenched with 10% aqueous citric acid (50 mL)
2. extractionThe mixture was extracted into dichloromethane (3×50 mL)
3. washthe dichloromethane solution was washed with 10% aqueous citric acid (40 mL)
4. dry with materialdried over Na2SO4
5. customAfter removing the solvent in vacuo
6. customthe residue was purified by flash column chromatography (dichloromethane)

ORD record

ord-387d7d2e2e734a53adb13ff6d236df96

Source dataset

uspto-grants-1999_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05891909